Last week the Biochemistry Department hosted Dr. Phillip Zamore from UMass Worcester to talk about the complexities of RNA interference at the molecular level, and what his lab has learned using Drosophila melanogaster as a model system. It was quite the seminar– dense and enthusiastically delivered. You should have been there!
For those of you who couldn’t be, two things in particular stirred up that good old sense of wonderment surrounding the reality that, for the most part, all the molecular events occurring in cells are successfully executed and keep us all swinging.
The first is related to the title of this blurb. In order for RNA interference to be carried out, a small interfering RNA (siRNA) must be matched to its target– a specific unlucky messenger RNA (mRNA) who will never grow up to be a protein. Once the siRNA has bound to the mRNA, degradation machinery sets to work “killing the messenger” and when it’s done the central dogma for this gene reads: DNA -> RNA -> nucleotide offal. Amazingly, this very specific search-and-destroy mission is carried out in the bustling cellular milieu with little else to go by other than base pair recognition. And just as the difficulty of such a task was beginning to sink in, Dr. Zamore told us that it is possible for siRNAs to find their specific target even when they only differ from another message by a single base pair.
The second is that Argonaute, the protein responsible for facilitating the pairing of an siRNA to its target mRNA, doesn’t just hold the siRNA like a limp noodle, but instead twists the linear molecule into a more energetically favorable shape that allows half of it to easily bind its target while keeping the other half out of the way until the first half has bound.
For more information about these interesting tidbits, see the following articles:
1. Designing siRNA that distinguish between genes that differ by a single nucleotide
