A few weeks ago I asked about the difference between microRNA and small interfering RNA. That was confusing enough. Now I need to know (for work) about how these small RNA’s affect gene regulation.
Need help here.
I think I understand two separate mechanisms.
small RNA coupled to some protein complex sits on the mRNA and effectively blocks the ribosome from producing the protein.
the small RNA in another protein complex (RISC?) forms a double stranded section with the mRNA, which is recognized by an enzyme that cuts the mRNA. THis cleaved mRNA is then cleaned up by the cell.
Is my understanding anywhere near correct? Is there any other mechanism that I’m missing?
Heh. The problem is that there’s only a handful of people here that know what you’re talking about, and none of us are really experts…
Off the top of my head, I believe the two mechanisms you mention are correct. However, IIRC there are still a number of other mechanisms. Wiki has a half-decent overview. And here’s a decent introductory review article in Science (subscription required).
Both of these mechanisms can happen with both types of small RNA. Hrm. I can’t find the presentation I made a while back that had a nice diagram, but there are a few other things small RNAs can do as well, as in this diagram. The small RNAs can target proteins to the DNA and lead to the gene itself being methylated or regulated in other ways. This is sometimes done in combination with mRNA degradation - as the fullsized mRNA is degraded, it generates new transient small RNAs upstream and downstream of the binding site of the original small RNA, and these new transient species can act in the same ways as the original - sort of a signal amplification step.
So off the top of my head, they can degrade target mRNAs, silencing the gene temporarily. They can sequester mRNAs so that ribosomes can’t translate them, but still keep them around for later use. They can target the DNA, leading to longer-lasting regulation via methylation or heterochromatin formation. Some of them (trans-acting siRNAs) can be secreted and travel to other cells to act there. I’m sure I’m missing some as well.
By chance, in today’s New England Journal of Medicine, there was a review article on some newer concepts in genomic medicine. One of the many sections I didn’t understand referenced this relatively recent review article on miRNAs and siRNAs from CELL which may be of some interest to you.
By the way, the NEJM article, itself, is free (or so it’s claimed on the site) and seems quite informative on many areas that have only recently come to the fore in genomics. Enjoy.
