Saturday, June 30, 2007

RNA tails and gene expression

Only a few years ago – definitely less than ten years – gene expression was thought to be a fairly simple process. One gene coded for one protein. The gene was "transcribed" from DNA to messenger RNA (mRNA), and in turn the mRNA was used to direct the manufacture of proteins in structures called ribosomes.

But then there were a series of "complications". Genes could be turned "on" or "off" by means of transcription factors, which are separate proteins produced by separate genes, and which are capable of either promoting or suppressing the transcription of other genes. Further, genes are not straight uninterrupted segments of DNA that correspond directly (via mRNA) to proteins, because genes contain segments called introns that are edited out of finished mRNA and ignored. And what is more, coding segments of genes (called exons) can be spliced together in different ways to produced finished mRNA (discussed here). This makes it possible to obtain multiple distinct proteins from a single gene.

And then, outside of the RNA transcription process, it turns out that small bits of RNA, called microRNA (miRNA) and small interfering RNA (siRNA), and which are coded for in parts of the genome long thought to be "junk", can become attached to mRNA and inhibit (or perhaps at times promote) production of proteins from it. (See this.) Nor should we forget to mention ribozymes, which can also mess around with mRNA. And if all that weren't enough, there are also a variety of epigenetic factors which can turn on or off entire segments of a genome.

Is that all? No. There are probably a number of other mechanisms that modify, regulate, and control gene expression – mechanisms as yet undiscovered. After all, there's a lot of "junk" DNA, whose function we still have no clue about – except that a lot of it isn't truly "junk".

Here's an example that has just come to light: RNA "tails".

Yeast: The Key To Understanding How Cells Work
The major contribution to the collaborative study by Associate Professor Preiss' Lab was to measure the length of polyadenosine "tails" on the messenger RNA (mRNA) molecules that are generated from each gene to serve as a blueprint in making proteins - the building blocks of life.

"One might think that a tail does not matter much, but with mRNAs it has a big impact on how long they stay around in cells and how much protein is made from them. In this way it is a case of the tail wagging the dog. Since nearly every mRNA in every human cell has these tails, it is not surprising that controlling their length turns out to be quite important. It is known to be involved in embryonic development and during learning and memory in the brain, for instance. The mRNA tails also seem to be the target for recently discovered tiny cellular brakes called microRNAs. Failure of these brakes contributes to human diseases, such as heart defects and cancer.


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