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Sophisticated RNA

January 4th, 2007 by Mike Gene

The non-teleological perspective views RNA as a primitive, ancient relic of the process of abiogenesis. The teleological perspective views RNA as a sophisticated molecule that plays an essential control function within the cell and has never existed apart from its cellular context.

While RNA is crucial to all living things, I think eukaryotes have more fully exploited its ability to control the proteome (a cell’s protein complement). A simple fact from cell biology explains this. In prokaryotes, the process of RNA synthesis (transcription) is coupled to the process of protein synthesis (translation). This allows bacteria to more efficiently express their genes and the bacterial cell design is all about efficiency. But eukaryotes trade efficiency for flexibility, and as such, have a nucleus where the genome is physically separated from the ribosomes. This means there is a much larger window of opportunity to process and modify protein-encoding RNA in eukaryotes, which in turn means the greater potential for control. One such control mechanism exploited by eukaryotes is alternative-splicing, where a single gene can give rise to dozens of gene products that are variations on a theme.

In his book, Muscles as Molecular and Metabolic Machines, Peter Hochacka wrote:

It is accepted that many (indeed most) of the components required for integrated muscle function are proteins, which usually can be expressed in more than one form (so-called isoforms, isoproteins, or isoenzymes). Isoforms of the components of muscle tissue are formed in a variety of ways: at the genetic level, with different genes specifying the different forms and timing of their expression; at the translation level, with different splicing patterns generating different isoforms; or at the post-translational level, with the modification of the gene polypeptide products generating different isoforms of those products. This means that, in principle, muscle cells could be put together in many different ways – in as many ways as there are combinations of the isoprotein components that together make up the tissue we call muscle.

A question that will arise over and over again in our analysis, therefore, will be whether or not all possible combinations are or ever can be realized. The answer to that question will invariably be negative. Indeed it will be argued that, in some of the most finely tuned and well adapted muscles, a single unique combination from the myriad of statistically possible combinations seems to be selected at the expense of all others.

Or as he explains later:

We suggest that the isoform design of the overall system is one reason why the realized number of muscle types is only a minute fraction of the maximum number theoretically possible. Just as the drive shaft of a sports car would not do in a cement truck, troponin c isoforms in fast muscles many not be suitable for slow muscles; fast muscle Ca ATPase may be debilitating to slow muscles, while slow muscle presynaptic Ca channels would simply not work well enough in fast muscle, and so forth.

While we can credit RNA and alternative splicing for generating most of these isoforms, what controls whether and where the RNA is spliced?

According to a recent study, RNA is again involved:

As reported in the January 1 issue of G&D, a UCLA research team led by Dr. Douglas Black has shown how microRNAs regulate alternative splicing during muscle development. The researchers determined that the muscle-specific microRNA miR-133 targets the alternative splicing factor, nPTB, during early myogenesis. The resulting decrease in nPTB protein levels alters the splicing of muscle-specific mRNAs in such a way as to promote muscle cell differentiation. The targeting of this splicing factor allows the microRNA to control a larger temporal program of muscle cell gene expression through not just the direct translational regulation of mRNAs, but also by altering the splicing of important mRNAs.

From the non-teleological perspective, RNA appeared before cellular physiology and genome-proteome interactions ever existed and was selected for the simple, myopic reason of self-replication. It’s quite a stroke of luck that the same molecule whose properties were shaped in this primitive setting have been able to play such an important role in the evolution of something as sophisticated as muscle tissue, helping cells reach “a single unique combination from the myriad of statistically possible combinations.”

Another perspective would allow us to view RNA as something that was deeply embedded within cells to faciliate their evolution.

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One Response

  1. RNA Interference - Telic Thoughts Says:

    […] I talked briefly about these little RNAs here and here. Now comes the animation that outlines the basic events associated such RNA. […]

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