In a way, you can think of the molecular workings of the cell like the Library of Congress. You need information storage – these are the books. In each book (chromosome or parts of a chromosome) contain the instructions (genes) needed to make products (proteins) the cell may need.
Each time you want to make a certain molecule, you must consult the book (chromosome) that has the correct instruction page (DNA gene). But you may be making many copies of your product in a short period, so one book might not be enough.
You could keep many copies of each book, maybe thousands, but this would take up too much room. The LOC already covers 2.1 million sq. feet (and that’s just one main building). What if you needed 1500 copies of One Good Turn (and interesting book about the history of the screw and screwdriver) because at some time or another, 1500 people wanted to learn how to build a square screwdriver?
To avoid this need for extra space, you make copies of pages (mRNA) from the books (chromosomes) that can be taken out of the library (nucleus) and used for making the products. Each time you want a product, a translator (tRNA and ribosome) must be used. This converts the copied instructions (mRNA) into a usable product (protein).
When one or several translations have been made, the copied instructions start to tear and get worn, and finally break down. Good thing we still have the original copy of the book stored in the nucleus… I mean library. We can go back and make more copies later if we need them. Humans are amateurs, we only have about 25,000 sets of instructions stored in 46 books, nowhere near the 155.3 million of the LOC.
Ever here of small nuclear RNAs, or micro RNAs, or plasmid DNAs for that matter? We have talked about plasmids as extrachromosomal pieces of DNA that can code for genes, especially antibiotic resistance genes in prokaryotes.
But the list of RNAs is far more impressive. There are regulatory RNAs that control gene expression (whether or not a protein is made from a gene), RNAs that control modification of other RNAs or work in DNA replication. There are even RNAs that are parasitic, like some viral genomes (RNA viruses) and retrotransposons.
Of these, retrotransposons may be the most interesting. A transposon is a piece of DNA that can jump around from place to place in the chromosomes of a cell. Barbara McClintock won a Nobel Prize for identifying transposable elements were responsible for the different colors of corn kernels in maize.
In and of themselves, retrotransposons represent an exception in nucleic acids. They are mRNA sequences that can turn back into DNA. Transcription is the process of using DNA to produce an mRNA, so going the opposite direction is called reverse transcription. This is also what retroviruses like HIV do.
In this way, retrotransposons can make more copies of themselves and end up all over the chromosomes of the organism. Mutation occurs at a higher rate in reverse transcription than in DNA replication because reverse transcriptase makes more mistakes than replication enzymes. This is why HIV is so hard to treat; it mutates so often that drug design can’t keep up with the changes in the viral proteins.
So how can the same mRNA sometimes be translated, and other times end up in a new place on the DNA? A 2013 study has investigated how one type of retrotransposon manages these different outcomes. The BARE retrotransposon of plants has just one coding sequence for a protein, but the study results show that it actually makes three distinct mRNAs from this one piece of DNA.
If plants have so much nucleic acid in the form of retrotransposons, could these be the remnants of ancient viral infections? You betcha, and it doesn’t stop with plants. In his fascinating book, The Violinist’s Thumb, Sam Kean lays out a compelling argument that most human DNA is actually just viral nucleic acid remnants, much of it being mutated versions of old RNAs.
Old RNA is probably the best way to describe all nucleic acids, because the generally accepted view of the evolution of life on Earth is that everything started with RNA. This called the RNA world hypothesis and professes that the job that DNA does now was first done by RNA.
The hypothesis also says that what those that protein enzymes now do - cutting things up, putting things together, and modifying existing structures - was originally done by RNAs as well, called catalytic RNAs.
We have evidence for this hypothesis, specifically, we know of many RNAs that have enzymatic activity. Called ribozymes (a cross between ribo for RNA, and zyme for enzyme), some RNAs carry out enzymatic roles in our cells and the cells of every eukaryote and prokaryote ever analyzed for their presence.
One essential ribozyme function is the synthesis of protein. The ribosome (a riboprotein because it is made up of many RNAs and proteins) translates the codons of mRNA into a sequence of amino acids. It uses the RNA to link the individual amino acids together via peptide bonds. I’d say that’s essential.
Other ribozymes work on themselves. Many mRNAs, when first copied from DNA have sequence within them that is not used in the final product. These are called intervening sequences (or introns), and are cut out (spliced) as part of the transcript processing. Group I and II introns are self-splicing. They fold over on themselves and cause their own excision from the RNA of which they are part!
Group I introns can be found in the mRNAs, rRNAs, and tRNAs of most prokaryotes and lower eukaryotes, but the only place we have found them so far in higher eukaroytes are the introns of plants and the introns of mitochondrial and chloroplasts genomes. Yet more evidence for the plastid endosymbiosis hypothesis.
If the RNA world hypothesis is to be strengthened, we must find a catalytic RNA that can replicate long strings of RNA “genes.” If RNA was both the storage material and the enzymatic material, there must have been an RNA-dependent, RNA polymerase that was itself a piece of RNA. An RNA replicase has not been found, probably because life moved on to using DNA as the long-term repository of genetic information, But we should be able to make an RNA replicase as a proof of concept.
Then a study was published showing that a modification of R18 could synthesize much longer strings and could replicate many different RNA templates. In this publication, the authors could synthesize ribonucleic acids of 95 bases, almost as long as the R18 replicase itself. Another study has shown that some catalytic RNAs can self-replicate at an exponential rate, making thousands of copies of themselves while still having catalytic function.
It seems that the RNA hypothesis is getting stronger, but there remain some hurdles.
A July, 2013 study shows that primitive protein enzymes (called urenzymes, where ur = primitive) activate tRNAs much faster than do ribozymes. These primitive proteins date to before the last common ancestor, so they have been around nearly as long as life itself. tRNA urenzymes suggest a tRNA-enzyme co-evolution, providing evidence that catalytic proteins and the conventional central dogma were important in early life – a result that does not support the RNA world hypothesis. I’m glad – the hunt goes on.
In the next weeks, let’s take a look at nucleic acid structures and their building blocks. Think DNA is double stranded? – not always. Think A, C, G, T, and U are the only nucleotides life uses? – not even close.
For more information or classroom activities, see:
Nucleic acids –
Central dogma of molecular biology –
Types of RNA –
RNA world hypothesis –
Catalytic RNA (ribozymes) –