miRNA controversy: translational inhibition versus mRNA destabilization

The Harvard Medical School Blog, it takes 30, recently wrote a post on the controversy surrounding microRNA’s mechanism of action. In a nutshell, the controversy surrounds whether or not microRNAs act by inhibiting mRNA translation or mRNA stability. The studies involved used what may be considered not so robust methodologies which may have clouded the accuracy of their results.

In any event, the issue is quite interesting for anyone involved in transcriptional/translational research and the post does a good job of sizing up the debate. Below is a short snippit from the post itself:

A recent paper from the Bartel and Weissman groups (Guo et al. Mammalian microRNAs predominantly act to decrease target mRNA levels, Nature 466 835-40, PMID: 20703300) provides an interesting snapshot of the journey of a field from consensus to controversy to (one day?) consensus again.

At issue is the question of how microRNAs — small RNAs that control gene expression — have their effect. Clearly they bind specifically to messenger RNAs that carry a short target sequence; clearly, the overall result is that a reduced amount of protein is expressed from the targeted mRNA. But is the translation of the mRNA blocked, or is the mRNA itself destabilized, or both? The answer could affect everything from the way you measure an miRNA effect to the way you think about choosing targets for therapeutic applications. And the consensus in the field seems to be swinging fairly hard — or has swung, depending on who you talk to — from one extreme (the main effect is on translation) almost all the way to the other (most, but not all, of the effect is due to mRNA destabilization).

For more information see the It takes 30 blog from the Department of Systems Biology @ Harvard Medical School

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