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Friday, January 12, 2007

Important Science
There's some good stuff being published this week in Nature and Science of broad appeal.

First a pair of papers, including one from recent Nobel laureate Andrew Fire, on siRNA and the existence of an RNA-dependent RNA polymerase (RdRP) activity with RNAi effects. Now, to make sense of that sentence. RNAi refers to the use of RNA molecules to inhibit translation of RNA into protein, either by destruction of the message (exact binding of siRNA to a sequence leads to the cutting of mRNAs), or by blocking translation (inexact binding of miRNAs to mRNA appears to prevent proteins from being translated from the mRNA message).

These papers are proposing at the very least a modification of the siRNA dogma, that is the siRNA binds to the mRNA because of its complementary sequence and leads to enzymatic cutting of the mRNA - thus destroying the transcript. Instead it lends support to an alternative hypothesis that there seemed to be evidence for for quite some time, that the siRNA binding to transcript leads to the formation of more short complementary RNA molecules, or secondary siRNAs, that increase the efficacy of the siRNA effect. The initial siRNA might not be responsible for digestion of the mRNA at all, and instead may just be a signal for RdRP to create the secondary siRNAs responsible for functional RNAi.

The second big news I like is that researchers have reported in Nature the discovery of a glucose sensor in the liver. This seems like an obvious thing for the body to have, but the fact that we only just found it shows how difficult it's been to discover. For the most part glucose concentration in the blood is thought to be controlled by insulin, but this represents a direct target of glucose in the liver that when activated by glucose controls genes involved in liver glucose metabolism and cholesterol homeostasis. It also may represent a new target for therapy not just for diabetes (Type II or adult diabetes more likely) but for also for cholesterol control.

Finally, Nature reports on the fate decisions in the early embryo and the histone modifications determine general fates of cells in the 4-cell stage. This is interesting because it represents a fairly new field called epigenetics - that is the study of modifications to DNA that transmits information without changing the DNA code itself. Therefore a gene might be active or inactive, not because of a promoter sequence that would ordinarily allow transcription, but because of small chemical changes to the DNA or the histone proteins that DNA is wrapped around. These authors show which modifications of histones are determining cell fates after the first two divisions of cells in a mammalian embryo, it's pretty amazing and reflects a distinct and powerful layer of control of gene expression above the genetic code that is critical from the very start of development.

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