We are searching data for your request:
Upon completion, a link will appear to access the found materials.
Of the 2 figures, which is the correct structure of RNA,
This is the link : 1: biol-2022/9720/image_pIpaoF0v7q9v.jpg">
Sorry, the figure is not to scale.
If there's any problem with the question please inform me.
Both figures include A,G,T,C.
Those are abbreviations for the bases adenine, guanine, thymine and cytosine.
RNA does not contain thymine, but its unmethylated form uracil, abbreviated with an U.
Thus, none of the structures represents RNA.
As Marzipanherz said, RNA does not contain thymine. Furthermore, none of those resemble any kind of RNA structure you usually see, for example two dimensional secondary structures showing watson-crick basepairing such as this example: http://www.rna-seqblog.com/wp-content/uploads/2014/02/secondary1.jpg">https://en.wikipedia.org/wiki/RNA After you've done this, you can e.g. go to the vienna webserver http://rna.tbi.univie.ac.at/cgi-bin/RNAWebSuite/RNAfold.cgi and predict secondary structures of your own RNA sequences.
Patrick has been teaching AP Biology for 14 years and is the winner of multiple teaching awards.
RNA Structure is a single strand composed of nucleotides. Unlike DNA it does not form a double helix shape, but it does contain a series of nitrogenous bases (adenine, uracil, guanine and cytosine). RNA can temporarily form hydrogen bonds between bases of two strands.
When people think about nucleic acids, they typically think of DNA but there's another molecule RNA which is just as important. It's the one that takes the information that's being stored in DNA and sends it out to the cell so that the cell can actually use that info- information. DNA is a really long molecule RNA is typically a shorter molecule but it's just as important as DNA. It's the workers that help carry out some of the information and instructions of the DNA and it's built together much like DNA is so let's take a closer look.
The basic building blocks that make up RNA are nucleotides just like with DNA. Just like DNA it has a phosphate group then gives it a strong negative charge, it has a five carbon sugars sometimes called a pentose and some kind of nitrogen containing base or nitrogenous base. Now one of the differences to bear in mind between DNA and RNA is what is that pentose sugar. Well deoxyribose and ribose are the two sugars. Deoxyribose can you guess which one uses that? You're right! DNA which stands for Deoxyribose Nucleic Acid while RNA Ribonucleic acid uses ribose and if you look at the names they look very similar in fact if I cover up the deoxy I see the word ribose, what does that mean? Well this is ribose notice down here on the second carbon there's an OH group or hydroxyl group for those who are doing Chemistry. If I pull off that oxygen i.e. deduct it, then I deoxygenated this ribose here and look all that's left is the hydrogen so that's the difference between ribose and deoxyribose sugar.
The other difference that you'll see in the structure of the nucleotides is that it uses the same guanine and adenine and cytosine that DNA uses but instead of using thymine uses a particular kind of pyrimidine called uracil. Now to join RNA molecules together it works pretty much the same way as joining DNA molecules together. You take our phosphate and sugar and nitrogenous base i.e. a nucleotide and you bring the phosphate group of the next one in and it joins a phosphate to that sugar and then you extend that and so you windup with a long strand of RNA nucleotides with their bases sticking out with the phosphates and sugars forming the backbone of the strand.
Now you're familiar with this with DNA and you know that DNA often twist up to form the very famous double helix. Well RNA can't do that but because without addition oxygen that's on this carbon right there it tends to make it unstable for long stretches to be in a double helical form. For short portions however you can and the way you can form an RNA to RNA strand or RNA to DNA strand follows the same base pairing rules that DNA does with a lot of twist. Remember that RNA does not use thymine it uses uracil. DNA if we're binding DNA to RNA and we have a RNA adenine here this would have to be a thymine for DNA but if I was making an RNA to RNA where I have an adenine I'll have to use uracil which you'd abbreviate u so if I have my RNa strand here that's a, c, a I follow the standard base pairing rules of a to t or u, g to c so here's the c there's a guanine or g. Here's an a I put a thymine so that's it pretty straight forward it's much like DNA just with those little differences one mnemonic or trick to help you remember the key difference of using uracil instead of thymine is remember what's the abbreviation for uracil, it will be the letter u so just think in your head you are correct and if you are, you are correct.
Role of RNA in Biology
RNA, in one form or another, touches nearly everything in a cell. RNA carries out a broad range of functions, from translating genetic information into the molecular machines and structures of the cell to regulating the activity of genes during development, cellular differentiation, and changing environments.
RNA is a unique polymer. Like DNA, it can bind with great specificity to either DNA or another RNA through complementary base pairing. It can also bind specific proteins or small molecules, and, remarkably, RNA can catalyze chemical reactions, including joining amino acids to make proteins.
All the RNA in cells are themselves copies of DNA sequences contained in the genes of a cell's chromosomes. Genes that are copied—"transcribed"—into the instructions for making individual proteins are often referred to as "coding genes." The genes that produce RNAs used for other purposes are therefore called "noncoding RNA" genes.
RNA molecules assemble proteins and modify other RNAs
Several key classes of RNA molecules help convert the information contained in the cell's DNA into functional gene products like proteins. Messenger RNAs (mRNAs) are copies of individual protein-coding genes, and serve as an amplified read-out of each gene's nucleic acid sequence. Two key noncoding RNAs participate in the assembly of the proteins specified by mRNAs. Ribosomal RNA (rRNA) constitutes the core structural and enzymatic framework of the ribosome, the machine that synthesizes proteins according to the instructions contained in the sequence of an mRNA. Transfer RNAs (tRNAs) use complementary base pairing to decode the three-letter "words" in the mRNA, each corresponding to an amino acid to be sequentially incorporated into a growing protein chain.
Most RNA molecules, once transcribed from the chromosomal DNA, require structural or chemical modifications before they can function. In eukaryotic cells, mRNAs are assembled from longer RNA transcripts by the spliceosome, which consists of spliceosomal RNAs and protein partners. Spliceosomal RNAs help discard intervening sequences (introns) from pre-mRNA transcripts and splice together the mRNA segments (exons) to create what can be a complex assortment of distinct protein-coding mRNAs from a single gene. Many noncoding RNAs also require post-transcriptional modifications. For instance, ribosomal RNAs receive numerous chemical modifications that are required for proper ribosome assembly and function. These modifications are introduced by protein enzymes in conjunction with specialized noncoding RNAs (called snoRNAs) that base pair with the rRNA and guide the modifying enzymes to precise locations on the rRNA.
Some RNAs possess intrinsic enzymatic activity and can directly catalyze RNA modification reactions. These catalytic RNAs include certain self-splicing RNA transcripts, ribozymes, and RNAse P, an RNA enzyme that trims the ends of tRNA precursors in essentially all cells.
RNA molecules regulate gene expression
Regulation of the production of proteins from coding genes is the basis for much of cellular and organismal structure, differentiation, and physiology. Diverse classes of noncoding RNAs participate in gene regulation at many levels, affecting the production, stability, or translation of specific mRNA gene products.
In prokaryotes (for example, bacteria), small antisense RNAs exert a variety of gene regulatory activities by base pairing specifically to their target mRNAs. Also common in prokaryotes are riboswitches, noncoding RNA sequences that usually function as regulatory domains contained within longer mRNAs. Riboswitches regulate the activity of their host mRNAs by binding to small molecules such as nucleotides or amino acids, sensing the abundance of those small molecules and regulating the genes that make or use them accordingly.
Eukaryotic cells contain thousands of small RNAs associated with various RNA interference (RNAi) pathways. For example, microRNAs (miRNAs) are regulatory RNAs approximately 22 nt long that are produced from longer transcripts that contain a certain kind of double-stranded "hairpin" structure. miRNAs associate with a protein of the Argonaute class, and base-pair specifically to mRNAs to inhibit their stability or translation. There are hundreds of miRNA genes in plants and animals, and each miRNA can regulate the activity of hundreds of protein-coding genes. Therefore, miRNAs individually and collectively have a profound impact on the development and physiology of multicellular eukaryotes.
Small interfering RNAs (siRNAs) are similar in length to microRNAs and are also associated with Argonaute proteins. Unlike miRNAs, which are produced from specific genetic loci that have evolved to regulate mRNAs, siRNAs can derive from essentially any transcribed region of the genome. siRNAs typically act directly upon the locus from which they are produced. So, siRNAs occur in cells where genes are under ongoing self-regulation by RNAi.
A major role for certain classes of small noncoding RNAs is defense of the cell against viruses, transposons, and other nucleic acid sequences that pose a potential threat to cellular homeostasis or genome stability. The response of some cells against viral infection includes the production of siRNAs complementary to the virus. Many endogenous siRNAs in eukaryotic cells specify the silencing of transposons and repeat sequences that are already resident in the genome. Similarly, in animals the Piwi-associated RNAs (piRNAs) promote genome integrity by silencing transposons and repeat sequences.
Another class of regulatory RNA consists of diverse kinds of longer noncoding transcripts that generally function to regulate the expression of distant genetic loci, often by suppressing or promoting their transcription. For example, the rox RNAs of the fruit fly seems to facilitate the remodeling of chromosome structure to allow the male X chromosome to be transcribed at twice the rate as a single X chromosome in females, which have two X's. Similarly, the Xist RNA in mammals helps inactivate one of the two X chromosomes in females, allowing males and females to have equivalent levels of gene expression from the X chromosome. Xist is one example of a broader class of very versatile regulatory RNAs known as long intergenic noncoding RNAs (lincRNAs). lincRNAs can act as scaffolds for the assembly of complexes of transcriptional regulatory proteins, and can facilitate the recruitment of defined combinations of protein regulators to specific genes.
This is an official Page of the University of Massachusetts Medical School
RNA Therapeutics Institute (RTI) &bull 368 Plantation St Worcester, Massachusetts 01605
By the end of this section, you will be able to do the following:
- Describe nucleic acids’ structure and define the two types of nucleic acids
- Explain DNA’s structure and role
- Explain RNA’s structure and roles
Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell’s genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) . DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes, the DNA is not enclosed in a membranous envelope.
The cell’s entire genetic content is its genome, and the study of genomes is genomics. In eukaryotic cells but not in prokaryotes, DNA forms a complex with histone proteins to form chromatin, the substance of eukaryotic chromosomes. A chromosome may contain tens of thousands of genes. Many genes contain the information to make protein products. Other genes code for RNA products. DNA controls all of the cellular activities by turning the genes “on” or “off.”
The other type of nucleic acid, RNA, is mostly involved in protein synthesis. The DNA molecules never leave the nucleus but instead use an intermediary to communicate with the rest of the cell. This intermediary is the messenger RNA (mRNA) . Other types of RNA—like rRNA, tRNA, and microRNA—are involved in protein synthesis and its regulation.
DNA and RNA are comprised of monomers that scientists call nucleotides . The nucleotides combine with each other to form a polynucleotide , DNA or RNA. Three components comprise each nucleotide: a nitrogenous base, a pentose (five-carbon) sugar, and a phosphate group ((Figure)). Each nitrogenous base in a nucleotide is attached to a sugar molecule, which is attached to one or more phosphate groups.
The nitrogenous bases, important components of nucleotides, are organic molecules and are so named because they contain carbon and nitrogen. They are bases because they contain an amino group that has the potential of binding an extra hydrogen, and thus decreasing the hydrogen ion concentration in its environment, making it more basic. Each nucleotide in DNA contains one of four possible nitrogenous bases: adenine (A), guanine (G) cytosine (C), and thymine (T).
Scientists classify adenine and guanine as purines . The purine’s primary structure is two carbon-nitrogen rings. Scientists classify cytosine, thymine, and uracil as pyrimidines which have a single carbon-nitrogen ring as their primary structure ((Figure)). Each of these basic carbon-nitrogen rings has different functional groups attached to it. In molecular biology shorthand, we know the nitrogenous bases by their symbols A, T, G, C, and U. DNA contains A, T, G, and C whereas, RNA contains A, U, G, and C.
The pentose sugar in DNA is deoxyribose, and in RNA, the sugar is ribose ((Figure)). The difference between the sugars is the presence of the hydroxyl group on the ribose’s second carbon and hydrogen on the deoxyribose’s second carbon. The carbon atoms of the sugar molecule are numbered as 1′, 2′, 3′, 4′, and 5′ (1′ is read as “one prime”). The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′–3′ phosphodiester linkage. A simple dehydration reaction like the other linkages connecting monomers in macromolecules does not form the phosphodiester linkage. Its formation involves removing two phosphate groups. A polynucleotide may have thousands of such phosphodiester linkages.
DNA Double-Helix Structure
DNA has a double-helix structure ((Figure)). The sugar and phosphate lie on the outside of the helix, forming the DNA’s backbone. The nitrogenous bases are stacked in the interior, like a pair of staircase steps. Hydrogen bonds bind the pairs to each other. Every base pair in the double helix is separated from the next base pair by 0.34 nm. The helix’s two strands run in opposite directions, meaning that the 5′ carbon end of one strand will face the 3′ carbon end of its matching strand. (Scientists call this an antiparallel orientation and is important to DNA replication and in many nucleic acid interactions.)
Only certain types of base pairing are allowed. For example, a certain purine can only pair with a certain pyrimidine. This means A can pair with T, and G can pair with C, as (Figure) shows. This is the base complementary rule. In other words, the DNA strands are complementary to each other. If the sequence of one strand is AATTGGCC, the complementary strand would have the sequence TTAACCGG. During DNA replication, each strand copies itself, resulting in a daughter DNA double helix containing one parental DNA strand and a newly synthesized strand.
A mutation occurs, and adenine replaces cytosine. What impact do you think this will have on the DNA structure?
Ribonucleic acid, or RNA, is mainly involved in the process of protein synthesis under the direction of DNA. RNA is usually single-stranded and is comprised of ribonucleotides that are linked by phosphodiester bonds. A ribonucleotide in the RNA chain contains ribose (the pentose sugar), one of the four nitrogenous bases (A, U, G, and C), and the phosphate group.
There are four major types of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and microRNA (miRNA). The first, mRNA, carries the message from DNA, which controls all of the cellular activities in a cell. If a cell requires synthesizing a certain protein, the gene for this product turns “on” and the messenger RNA synthesizes in the nucleus. The RNA base sequence is complementary to the DNA’s coding sequence from which it has been copied. However, in RNA, the base T is absent and U is present instead. If the DNA strand has a sequence AATTGCGC, the sequence of the complementary RNA is UUAACGCG. In the cytoplasm, the mRNA interacts with ribosomes and other cellular machinery ((Figure)).
The mRNA is read in sets of three bases known as codons. Each codon codes for a single amino acid. In this way, the mRNA is read and the protein product is made. Ribosomal RNA (rRNA) is a major constituent of ribosomes on which the mRNA binds. The rRNA ensures the proper alignment of the mRNA and the Ribosomes. The ribosome’s rRNA also has an enzymatic activity (peptidyl transferase) and catalyzes peptide bond formation between two aligned amino acids. Transfer RNA (tRNA) is one of the smallest of the four types of RNA, usually 70–90 nucleotides long. It carries the correct amino acid to the protein synthesis site. It is the base pairing between the tRNA and mRNA that allows for the correct amino acid to insert itself in the polypeptide chain. MicroRNAs are the smallest RNA molecules and their role involves regulating gene expression by interfering with the expression of certain mRNA messages. (Figure) summarizes DNA and RNA features.
|DNA and RNA Features|
|Function||Carries genetic information||Involved in protein synthesis|
|Location||Remains in the nucleus||Leaves the nucleus|
|Structure||Double helix||Usually single-stranded|
|Pyrimidines||Cytosine, thymine||Cytosine, uracil|
|Purines||Adenine, guanine||Adenine, guanine|
Even though the RNA is single stranded, most RNA types show extensive intramolecular base pairing between complementary sequences, creating a predictable three-dimensional structure essential for their function.
As you have learned, information flow in an organism takes place from DNA to RNA to protein. DNA dictates the structure of mRNA in a process scientists call transcription , and RNA dictates the protein’s structure in a process scientists call translation . This is the Central Dogma of Life, which holds true for all organisms however, exceptions to the rule occur in connection with viral infections.
To learn more about DNA, explore the Howard Hughes Medical Institute BioInteractive resources on DNA (videos, animations, interactives).
Nucleic acids are molecules comprised of nucleotides that direct cellular activities such as cell division and protein synthesis. Pentose sugar, a nitrogenous base, and a phosphate group comprise each nucleotide. There are two types of nucleic acids: DNA and RNA. DNA carries the cell’s genetic blueprint and passes it on from parents to offspring (in the form of chromosomes). It has a double-helical structure with the two strands running in opposite directions, connected by hydrogen bonds, and complementary to each other. RNA is a single-stranded polymer composed of linked nucleotides made up of a pentose sugar (ribose), a nitrogenous base, and a phosphate group. RNA is involved in protein synthesis and its regulation. Messenger RNA (mRNA) copies from the DNA, exports itself from the nucleus to the cytoplasm, and contains information for constructing proteins. Ribosomal RNA (rRNA) is a part of the ribosomes at the site of protein synthesis whereas, transfer RNA (tRNA) carries the amino acid to the site of protein synthesis. The microRNA regulates using mRNA for protein synthesis.
(Figure) A mutation occurs, and cytosine is replaced with adenine. What impact do you think this will have on the DNA structure?
(Figure) Adenine is larger than cytosine and will not be able to base pair properly with the guanine on the opposing strand. This will cause the DNA to bulge. DNA repair enzymes may recognize the bulge and replace the incorrect nucleotide.
What are the structural differences between RNA and DNA?
DNA has a double-helix structure. The sugar and the phosphate are on the outside of the helix and the nitrogenous bases are in the interior. The monomers of DNA are nucleotides containing deoxyribose, one of the four nitrogenous bases (A, T, G and C), and a phosphate group. RNA is usually single-stranded and is made of ribonucleotides that are linked by phosphodiester linkages. A ribonucleotide contains ribose (the pentose sugar), one of the four nitrogenous bases (A,U, G, and C), and the phosphate group.
What are the four types of RNA and how do they function?
The four types of RNA are messenger RNA, ribosomal RNA, transfer RNA, and microRNA. Messenger RNA carries the information from the DNA that controls all cellular activities. The mRNA binds to the ribosomes that are constructed of proteins and rRNA, and tRNA transfers the correct amino acid to the site of protein synthesis. microRNA regulates the availability of mRNA for translation.
Why is RNA important?
DNA and RNA are ancient, but their discovery was relatively recent. In 1869, chemist Friedrich Miescher documented a kind of molecule that had never been studied before—nucleic acid. It wasn’t until around the 1930s that the term DNA began to be used, with RNA following in the 1940s. In the 1950s, the work of biophysicist Rosalind Franklin and biologists James Watson and Francis Crick revealed DNA’s double helix structure. The function of RNA began to be further understood during the 1950s and 60s as scientists began to understand the role of messenger RNA.
This understanding is still developing. Until quite recently, RNA’s role was thought to be largely limited to assisting with protein synthesis in its forms as messenger RNA, transfer RNA, and ribosomal RNA. However, scientists are continuing to discover new types of RNA and more functions that RNA performs in the body. For example, recent discoveries suggest that there are several types of RNA that regulate how many proteins the ribosomes produce.
Types of RNA
EQUINOX GRAPHICS / Science Photo Library / Getty Images
RNA molecules are produced in the nucleus of our cells and can also be found in the cytoplasm. The three primary types of RNA molecules are messenger RNA, transfer RNA and ribosomal RNA.
- Messenger RNA (mRNA) plays an important role in the transcription of DNA. Transcription is the process in protein synthesis that involves copying the genetic information contained within DNA into an RNA message. During transcription, certain proteins called transcription factors unwind the DNA strand and allow the enzyme RNA polymerase to transcribe only a single strand of DNA. DNA contains the four nucleotide bases adenine (A), guanine (G), cytosine (C) and thymine (T) which are paired together (A-T and C-G). When RNA polymerase transcribes the DNA into a mRNA molecule, adenine pairs with uracil and cytosine pairs with guanine (A-U and C-G). At the end of transcription, mRNA is transported to the cytoplasm for the completion of protein synthesis.
- Transfer RNA (tRNA) plays an important role in the translation portion of protein synthesis. Its job is to translate the message within the nucleotide sequences of mRNA into specific amino acid sequences. The amino acid sequences are joined together to form a protein. Transfer RNA is shaped like a clover leaf with three hairpin loops. It contains an amino acid attachment site on one end and a special section in the middle loop called the anticodon site. The anticodon recognizes a specific area on mRNA called a codon. A codon consists of three continuous nucleotide bases that code for an amino acid or signal the end of translation. Transfer RNA along with ribosomes read the mRNA codons and produce a polypeptide chain. The polypeptide chain undergoes several modifications before becoming a fully functioning protein.
- Ribosomal RNA (rRNA) is a component of cell organelles called ribosomes. A ribosome consists of ribosomal proteins and rRNA. Ribosomes are typically composed of two subunits: a large subunit and a small subunit. Ribosomal subunits are synthesized in the nucleus by the nucleolus. Ribosomes contain a binding site for mRNA and two binding sites for tRNA located in the large ribosomal subunit. During translation, a small ribosomal subunit attaches to a mRNA molecule. At the same time, an initiator tRNA molecule recognizes and binds to a specific codon sequence on the same mRNA molecule. A large ribosomal subunit then joins the newly formed complex. Both ribosomal subunits travel along the mRNA molecule translating the codons on mRNA into a polypeptide chain as they go. Ribosomal RNA is responsible for creating the peptide bonds between the amino acids in the polypeptide chain. When a termination codon is reached on the mRNA molecule, the translation process ends. The polypeptide chain is released from the tRNA molecule and the ribosome splits back into large and small subunits.
Award presentation by Harold Varmus
Most Lasker Prizes celebrate great discoveries by honoring those most responsible for making them. But the Special Achievement award celebrates great people who have met an especially imposing standard: their work and character inspire “the deepest feelings of awe and respect within the biomedical community.”
In 1969, nearly fifty years ago, when Joan was a post-doctoral fellow at the Laboratory of Molecular Biology in Cambridge, England, she visited the NIH to give a lecture about her recent work. I was then, like some others on this podium, a recently trained physician trying to learn the rudiments of modern biology while doing government service during the Vietnam War. Joan was already well beyond the rudiments, exploring ideas I hadn’t even thought about, with methods I didn’t know. Despite her youth, she spoke with a clarity and self-assurance that already prompted respect, even awe.
My job today is to tell you how she got to that point—and how she has sustained the performance for another five decades. To do that succinctly, I need a rhetorical device. One of her many fans has written that she is a “persuasive missionary for molecular biology.” The phrase is accurate, but too limited, in ways I will illustrate. Still, it helps me frame her story: the origins of her faith in science and evidence her training in the “high church” of molecular biology the revelations that allowed her to expand its doctrines and the passions that brought others to embrace her broader view of life’s mysteries and to build a more diverse scientific community.
Let’s begin with her baptism. Sara Hall, a physics teacher at the Northrup Collegiate School in Minneapolis, encouraged Joan to build an oscilloscope and introduced her to the joys of collecting data. (Incidentally, Sara Hall also taught Marcia McNutt, now president of the National Academy of Sciences. We need more Sara Halls!)
In choosing a college to study science, Joan was influenced by her father, a high school guidance counselor with an abiding faith in practical applications of learning, as embodied in the Antioch College work-study program. In 1961, that program gave Joan her first encounter with molecular biology, when she was apprenticed to one of its early acolytes, Alex Rich, at MIT.
Long and frustrating hours at a spectroscope, trying to make ribosomes behave physically like DNA, as Alex hoped, did not dampen her enthusiasm for a career in science. But she didn’t see any successful women with independent scientific careers. Medicine seemed a bit more promising, so she applied to (and was accepted by) Harvard Medical School. But between her graduation from Antioch and matriculation at medical school, she had a productive time working with Joe Gall—a cell biologist (who, incidentally, also received this award a few years ago). So, when a single place suddenly opened up for a biology graduate student at Harvard and was offered to her, she took it.
Not all the faculty welcomed her, the sole women in her class. But some of the leading clergy in her new field were supportive: Jim Watson, Wally Gilbert, and her former mentor at MIT, Alex Rich. Watson accepted her in his group and encouraged her to do independent work on bacterial viruses. Later, he and others used their priestly contacts—with Francis Crick, Fred Sanger, Sidney Brenner, Mark Bretscher—to help her obtain a position at the Laboratory of Molecular Biology in Cambridge—the temple where her new husband, Tom Steitz, was determined to train with the world’s best structural biologists. And to become one himself (which, as we all know, he did).
At this time, just fifteen years after the revelation of the double helical structure of DNA, the doctrine of molecular biology was dominated by Crick’s Central Dogma. In the catechism, information flowed from DNA to RNA to protein it was encoded in triplets of four letters and the message, transcribed from DNA to RNA, was translated by ribosomes to make proteins. These tenets were profound, correct, and essentially universal. But was that all we needed to know?
The work that I heard Joan describe at NIH in 1969 was among the first to indicate that DNA and RNA did more than dictate the order of amino acids in proteins. In the experiments she had performed, independently and courageously, ribosomes were also being told where to sit on the RNA message to begin making proteins.
After Joan and Tom accepted independent positions at Yale, she persisted. And she discovered how RNA in the ribosome perceives novel signals in messenger RNA to find the place to start protein synthesis.
But that was just the beginning. Other kinds of RNAs seemed to be doing important things, conveying significant signals, without encoding proteins or without even getting to the cytoplasm (the place where proteins are made in eukaryotic cells). Some small RNAs were already known to transfer amino acids into proteins to execute the dictates of the Central Dogma. But Joan and her Yale students found that many other small RNAs appeared to work in realms beyond the Dogma these were often associated with specific but still mysterious proteins, forming protein-RNA complexes of uncertain purpose.
In one especially significant set of studies, Joan and a student, Michael Lerner, discovered that patients with auto-immune diseases made antibodies that reacted with subsets of those complexes. This deepened our understanding of some important diseases, like lupus erythematosis, but also helped to categorize the RNA-protein complexes, allowing systematic study. Some of the particles recognized novel signals in RNA sequences and were able to knit together parts of newly synthesized RNA, accurately forming the mature, spliced molecules that are then read by ribosomes to make proteins.
These and many other unexpected properties of RNAs—produced by all kinds of cells and by many pathogenic viruses—provided founding principles for an imposing new wing of the church of molecular biology. These were not heresies, and did not produce schisms. Instead they were “new testaments” that convey biological complexity. Together they have helped to change our thinking about living systems and their origins. They have inspired a vision in which RNA, not DNA, is central to the history of life.
At a more pragmatic level that Joan’s father would have appreciated, this vision became the defining element of a scientific club—a very “nice” club, as Joan is fond of saying—in which RNA and its novel features are the central objects of inquiry.
The discoveries I’ve been describing go well beyond what a missionary is expected to do for a church. But Joan has also excelled in the missionary’s central role: the recruitment and training of disciples. Virtually every Yale undergraduate who has dipped a toe in modern biology extols Joan’s lectures. Many have also been taken into her laboratory to taste what she cares about most—the gathering and interpretation of data—just as Sara Hall once did for Joan. These students and more senior trainees are united in praise for her virtues as a mentor: her enthusiasm for results, her rigor in interpreting them, and her integrity in allocating credit. For instance, she often returns the favor that her own mentors conferred on her—by allowing work done independently by trainees in her lab to be independently authored.
To this point in my introduction, I have been nearly gender-neutral. Joan’s achievements would be remarkable for anyone, regardless of gender. But this moment should not pass without recognizing the effects of her career on the status of women in science, including molecular biology.
Most churches begin as patriarchies, not necessarily maliciously but that cannot persist without grievous loss. Early in life, Joan was nearly lost to science because she didn’t see a path to an independent career. But, against odds, she has cut a trail that others can follow. Because she knows the significance of this trail, she has worked, locally and nationally, to make it better marked for those who might take it and better appreciated for the joys it can bring.
In that sense, today’s award for “special achievement” takes on even greater meaning and importance.
In the appropriate cell type and at the correct developmental stage, ribonucleic acid (RNA) polymerase transcribes an RNA copy of a gene, the primary transcript. However, the primary transcript may contain many more nucleotides than are needed to create the intended protein. In addition, the primary transcript is vulnerable to breakdown by RNA-degrading enzymes.
Before the primary transcript can be used to guide protein synthesis, it must be processed into a mature transcript, called messenger RNA (mRNA). This is especially true in eukaryotic cells . Processing events include protection of both ends of the transcript and removal of intervening nonprotein-coding regions.
On an RNA molecule, the end formed earliest is known as the 5 (5-prime) end, whereas the trailing end is the 3 end. The ends of the primary transcript are particularly susceptible to a class of degradative enzymes called exonucleases. During processing, the 5 end of the primary transcript is protected against the effects of these enzymes by the addition of a CAP. The CAP uses an unusual linkage between nucleotides. Exonucleases do not recognize this unusual structure and therefore cannot remove the CAP. Since exonucleases work only from an end, if the CAP nucleotide cannot be removed, the entire 5 end of the mRNA is protected. The 5 CAP also aids in transport out of the nucleus and helps bind the mRNA to the ribosome .
To protect the 3 end against degradative exonucleases, a poly-A tail is added by poly-A polymerase. Poly-A is a chain of adenine nucleotides, one hundred to two hundred units long. The poly-A tail has typical bonds that are susceptible to degradation by exonucleases, but it does not have any protein coding function so it does not particularly matter if some of the A
The most striking event in RNA processing occurs because the protein coding region in eukaryotic genes is not continuous. A typical eukaryotic gene is composed of a number of protein coding regions, called exons, that are separated by noncoding regions called introns. In fact, the number of nucleotides in the introns can be much larger than the number of nucleotides in the combined exons. The DNA gene contains the code for both the exons and the introns, as does the primary RNA transcript, but the noncoding intron sequences must be removed to form the mRNA before protein synthesis.
The process by which introns are removed and exons are joined to one another is called RNA splicing, and it is catalyzed by complexes of proteins and RNA called SNuRPs (small nuclear ribonucleoprotein particles). These complexes locate special RNA sequences that flank the exon/intron junctions, bind to them, and catalyze the splicing reactions. Some primary transcripts can be spliced in a few different ways. Such Ȫlternate splicing" yields a range of related proteins.
After addition of the CAP to the 5 end, the poly-A tail to the 3 end, and splicing of the introns, the processing is complete and the mRNA is transported through nuclear pores to the cytoplasm of the eukaryotic cell where translation (protein synthesis) will occur.
We thank Prof. Giles Oldroyd (SLCU, Cambridge), Dame Prof. Caroline Dean (John Innes Centre), Sir Prof. Shankar Balasubramanian (U. Cambridge), Prof. Alison Smith (John Innes Centre) and Dr. Desmond Bradley (John Innes Centre) for the discussions with this work.
Peer review information
Yixin Yao was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
The review history is available as Additional file 3.
Structure of the full SARS-CoV-2 RNA genome in infected cells
SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs or vaccines with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on predicted RNA structures in SARS-CoV-2 and most putative regulatory sequences are uncharacterized. Here we report the secondary structure of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq). Our results reveal previously undescribed structures within critical regulatory elements such as the genomic transcription-regulating sequences (TRSs). Contrary to previous studies, our in-cell data show that the structure of the frameshift element, which is a major drug target, is drastically different from prevailing in vitro models. The genomic structure detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.