Are you feeling a chill?

January 23, 2010

One of the interesting aspects of RNA biology is the functioning of structured RNAs as regulatory elements, in particular as sensors that detect changes in environment and transduce the information into a change in gene expression.  One interesting class of such RNAs are the so-called riboswitches.  These are RNAs that typically bind to a ligand, much as an in vitro-selected RNA may bind to a chemical (such as an amino acid). Binding changes the structure of the RNA, leading to changes in transcription, stability of the RNA, or translatability of the RNA.

Riboswitches may bind small molecule ligands.  Alternatively, they may sense temperature.  This occurs because many RNA structures can be rather sensitive to changes in temperature, owing to the tendency of some secondary structures to become disrupted at physiologically meaningful temperatures.  A recent study extends the realm of RNA thermometers to include the sensing of cold temperatures, and adds a new twist to the nature of the riboswitch.  In this study, the authors studied the regulatory motif of the E. coli cspA gene; this gene is a cold-shock gene, whose expression increases with lower temperature.  This regulation may be attributed to in part to the 5′-untranslated part of the cspA mRNA. This work showed that low temperature promotes an RNA fold that enhances translation and RNA stability. Interestingly, this fold requires much (most) of the cspA mRNA; in other words, the whole mRNA is a sort of RNA thermometer that senses low temperature. The authors propose that the structural variations reflect co-transcriptional folding of the RNA, and that two different pathways (and end products) are traversed in cells growing at normal and low temperatures.

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Signature in the Cell?

January 3, 2010

There is much abuzz in the ID-o-sphere regarding Stephen Meyer’s new book, “Signature in the Cell: DNA and the Evidence for Intelligent Design”.  The book is a lengthy recapitulation of the main themes that ID proponents have been talking about for the past 15 years or so; indeed, there will be precious little that is new for seasoned veterans of the internet discussions and staged debates that have occurred over the years.

Long though the book is, it is built around one central theme – the idea that the genetic code harbors evidence for design.  Indeed, the genetic code – the triplet-amino acid correspondence that is seen in life – is the “Signature in the Cell”.  Meyer contends that the genetic code cannot have originated without the intervention of intelligence, that physics and chemistry cannot on their own accords account for the origin of the code.

It is this context that a recent paper by Yarus et al. (Yarus M, Widmann JJ, Knight R, 2009, RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code, J Mol Evol  69:406–429) merits discussion.  This paper sums up several avenues of investigation into the mode of RNA-amino acid interaction, and places the body of work into an interesting light with respect to the origin of the genetic code.  The bottom line, in terms that relate to Meyer’s book, is that chemistry and physics (to use Meyer’s phraseology) can account for the origin of the genetic code.  In other words, the very heart of Meyer’s thesis (and his book) is wrong.

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The importance of poly(A) site choice

January 1, 2010

To ring out 2009, a brief mention of some studies that reinforce the conclusions mentioned in this essay.  The basic theme – it looks more and more as if poly(A) site choice can vary for many, many genes in humans, and that a general trend towards shorter 3’-untranslated regions(due to selection of poly(A) sites nearer the 5’ end of the mRNA) is seen in rapidly growing cells (such as stem cells and cancer cells). The consequences of this seem to be significant, as it seems as if shorter RNAs are more abundant, owing to an absence of RNA sequences that destabilize the mRNA.  In other words:  shorter 3′ UTRs = higher expression = more growth/less regulation.

The means by which such global trends in poly(A) site choice may be accomplished are not clear; this will undoubtedly be one of the areas of interest in the field of polyadenylation over the next few years.

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