I know some of you Dopers know a lot about genetics (Collounsbury!) so I was wondering if you could help me out. I’m a newspaper reporter, and I was assigned to do a profile of Thomas Cech, who won a 1989 Nobel Prize for discovering that RNA can act as an enzyme. The trouble is, I don’t know what the heck that means! I’ve searched the library, but I’ve been having trouble finding basic RNA info that’s aimed at laypeople like me. So, does RNA have its Stephen Jay Gould or Carl Sagan? The science isn’t the main focus of the article, so the reference material doesn’t have to be extremely detailed, but I’d like to be less than totally clueless when I interview Dr. Cech.
Proteins are made of amino acids. To make a specific protein, the cell must get the right amino acids in the right order according to the DNA’s instructions. Protein production begins with a process called transcription. That’s when enzymes break apart the two strands of DNA within a gene and assemble a molecule similar to DNA, called ribonucleicacid (RNA), along one of the open strands. This complementary copy of the gene, called messenger RNA (mRNA), then travels out of the nucleus and into the cell’s cytoplasm to deliver the blue prints. During gene translation, the mRNA directs the assembly of amino acids into proteins according to the gene’s nucleotide sequence.
I think Bear left out the last part, which I believe is when RNA acts as an enzyme. An enzyme is, of course, a catalyst for some reaction or process. It is not the mRNA that attaches to the ribosomes to produce the amino acids, but another RNA, called the transfer RNA (tRNA). It is the TRNA which acts like an enzyme, enabling the nucleic acids to form in the proper sequence to code for the appropriate amino acids. The ribosome is actually the nucleus for the production of protein, but the tRNA acts as an enzyme in the process.
I’m not an expert in this field and someone who is better learned here can give you more details, but that is the general process.
A lot of the important things in the human body include protein. Collagen is an important part of cartilage, bones and tendons. Hemoglobin helps carry oxygen in the blood. Your body also depends on a lot of chemical reactions occuring efficiently. Enzymes are helpers that allow these reactions to occur quickly and with minimal energy. It was long thought that all of these enzymes were proteins as well. Furthermore, each enzyme was though to come from a different gene. The discovery that RNA, a non-protein, could act as an enzyme was surprising and refuted the “one gene…one protein…one enzyme” theory.
Proteins are made from long chains of amino acids. People have about 20 different flavours of amino acid. To make a protein that works, the chain of amino acids needs to be folded and processed.
Genes are located in DNA. The DNA is made of two pieces which fit together. By taking the strands of DNA apart, a copy of the DNA can be made using either of the pieces as a template.
There are three types of RNA. Messenger RNA (mRNA) is the copy of the gene used to make a protein. It copies the DNA template in the nucleus, then goes into the fluid surrounding the cell, called the cytoplasm.
The cytoplasm contains little machines called ribosomes. These are machines that make protein once they have the blueprints. Ribosomes are made out of ribosomal RNA (rRNA). mRNA is the blueprint, rRNA is the factory. Materials are needed to make a protein. These are free amino acids, which are carried to the factory by transfer RNA (tRNA), which acts as a supplier.
OK, you’ve seen DNA described as a ladder? There’s two strands, with “rungs” made of pair of nucleotides. These nucleotides come in four varieties, called A, T, C, and G, and are always paired in a certain way (A to T and C to G), so if you split the ladder down the middle, each individual strand carries the same information as the original.
The DNA never leaves the nucleus of the cell, and the machinary to make the proteins from the blueprints (called ribosomes) is outside the nucleus, so you need to get a copy of the blueprints out to the ribosomes. This is where RNA comes in. A section of DNA “unzips”, and a strand of mRNA (messenger RNA) forms alongside one of the rungs, matching up to it. Once it’s assembled, it detaches from the DNA and heads out of the nucleus. Using various other sorts of RNA, the ribosome then uses the instructions to assemble a protein.
All that is the primary function of RNA in modern organisms. In the earliest life, the situation is a bit more complex. Biology had long been plagued by a sort of chicken-egg problem with DNA and proteins. Proteins are assembled according to the instructions in DNA, but DNA needs certain proteins called enzymes in order to reproduce. How could one exist without the other? The answer seems to be that it was neither DNA nor protein that came first, but RNA, which can both carry genetic information and, apparently, produce forms which are useable as enzymes.
First of all, one correction: tRNA does not act enzymatically. rRNA probably does, but more on that later.
The various functions of RNA have been addressed pretty well already. So - about the “RNA acting as enzymes” bit. All known natural enzymes (with the possible exception of rRNA) are proteins. The three dimensional structure of the amino acids that make up the enzyme is such that it is able to bind certain chemicals and affect their chemistry. Each enzyme has a different function - it binds specific substrates and creates specific products. Clear so far?
Now, remember that what allows it to do this is its three dimensional structure. There’s nothing really special about the amino acids themselves - it’s the shape they take that’s interesting. This means that you should be able to make an enzyme out of other kinds of molecules too. Cech’s discovery was of a synthetic RNA molecule that was able to catalyze a reaction. In other words, it acts like an enzyme. Because of base-pairing between the bases in the strand, it adopted a three-dimensional configuration that allowed it to catalyze some reaction (I forget what it was). The term “ribozyme” has been coined for this type of molecule.
So what? Why does this matter? Well, one of the biggest questions in biology is that of how life managed to set up the genetic code through evolution. How did DNA and protein get together and decide that proteins would be made according to DNA’s instructions? It had been speculated that RNA had probably been around longer than DNA. This discovery prompts some interesting speculation about how life started. If RNA can catalyze reactions and hold genetic information, it could be the link between DNA and proteins. The idea, then, would be that as life evolved, proteins would have taked over as enzymes and DNA as the genetic material, since both are better at their respective functions than RNA is.
A major weakness of this theory is that no ribozymes have been found in nature. This can be explained by the fact that, as I said, the other molecules are better at their jobs, but still, it would be nice to find some evidence. This is where rRNA comes in. The ribosome is composed of both rRNA and proteins, in (very roughly) equal proportions. It had been assumed that the proteins catalyzed the actual reactions, but then someone proved that the rRNA by itself could do it, thus providing evidence for natural ribozymes. The fact that every known living organism uses this system suggests that it evolved very early on, supporting the idea that RNA was the original model of life.
This Web site is a must for anybody into bio resaerch. Since you’re a reporter and just looking for info and not actual papers, adding review as a keyword will narrow your results.
Smeghead–did I get your post right? Ribozymes have not been found in nature? You have to be kidding? Right? Actually I read the preview of my post and I now believe you are being satirical. Tell me I’m buzzed and you’re trolling.
I just happened to hear a series of lectures by Peter Moore about the strucure of the ribosome. In his view the proteins are a part of structural scaffold, and are not even invovled with catalysis of the animo acid synthesis of a polypeptide. Basically, a ribosome is a ribozyme.
Let me know if I’m way off base here, but give me some cites. If you’re just pulling our legs’, well, I fell for it.
Wow, I was expecting a few references and I get this. Truly, this is a board dedicated to fighting ignorance.
Everyone’s comments were helpful (except for the disagreements–tell us the truth, Smeghead!). One thing I might not have made clear in my OP, though, is that I was hoping to find some sources on this that were written for the mass audience. The link 647 provided seems mainly to catalog scientific journals, which I must admit are mostly over my head. With all the attention paid to genetics lately, I assumed there must be some more accessible books out there on the subject. Or are there?
First I’d try my local public library. Looking for books on biology or evolution will usually give you more ‘beginner’ information than the books on Genetics specifically, but any books in most public library will usually be aimed at the general public. If that is insufficient go to a college library. I assume they’re as open in the States as they are here. Look for first year texts. Again books on Biology generally will usually be more user freindly than specific texts. That should give you a good amount of basic info. And of course you know everyone here will welcome any further questions.
Good Luck
PS When’s the interview?
Gaspode, I did go to the library, as I said in my OP, but now I think I was searching the catalog too specifically–I looked under RNA as a topic, which led me to some highly technical stuff. I don’t know where you live, but university libraries aren’t very open here. I don’t think I could even go back to the Stanford library, even though I’m an alumna, because my ID expired a few months after I graduated. I’m not sure why they’re so paranoid–maybe because the public libraries seem to attract people who are a few French fries short of a Happy Meal, as we say in the States.
One of the August 2000 (IIRC)issues of Science focuses on ribosomes and the latest developments regarding their structure, such as X-ray crystallography done by Peter Moore out of Yale, and others.
But self-splicing of mRNA could be considered catalytic, no ribosome invovled there.
It’s just a basic DNA intro. It’s pretty well done though.
The following is an article by Cech himself. Cech Article
On a sidenote, does anyone know anything about ribosomes and translation in e. Coli? I have a pretty specific question that I don’t want to float out there unless I have the correct audience.
Well, what’s the the question? It looks like some Dopers out there known their stuff.
Also, how does a peptide like Thyrotropin releasing hormone get pushed out of the ribosome? TRH is only 3 amino acids in length and the exit channel of the ribosome (In eukaryotes, at least)from catalytic site to exit hole is something like the equivalent of 50 amino acids in distance.
Is it synthesized as a longer pre-pro-hormone? Maybe, but what mechanisms move a short peptide chain throught the ribosome?
My cup of tea. I just wrote a qualifier on stuff similar to this.
Tom Cech was researching splicing. After a gene is transcribed into RNA, the RNA is processed by splicing to take out padding regions in the middle of the gene. Cech was looking to purify a nuclear extract which carried out splicing in a test tube. He found one kind of intron which would excise itself even in his negative control (only the RNA added with no extract). So, he won his Nobel by doing a control.
These type I autocatalytic introns are found in several genes. They have a characteristic sequence. They only depend on free G nucleotides’ 3’ hydroxyl group to provide a nucleophile for the strand cleavage. Alignment and transesterification follow by RNA secondary structure.
Other types of autocatalytic introns have been found. Another class of introns has been found to be involved in RNA editing. Another class can polymerize new RNA. And as you mentioned, the ribosome and the spliceosome are thought to work mainly on their RNA components.
Oh, I am getting a PhD in molecular genetics. I have also completed 2 years of medical school… I should know most of this stuff cold if people have more specific questions.
I am not too sure about TRH, but many hypothalamic factors are synthesized as prohormones, which are cleaved post-translationally. This is true with beta-endorphin, CLIP, MSH, ACTH, and some others which are synthesized as POMC (proopiomelanocortin). Is TRH a complete 3 codon open reading frame? I will do some research.
In translation in e. coli does the ribosome complex bind to the mRNA BEFORE the start codon and then scan down the sequence to find the start codon?
If so, how lengthy can the sequence prior to the start codon be? Would too lengthy of a sequence cause the ribosomal complex to fail to reach the Methionine?
