I’ve previously thought that these are two names for the same thing. Now I’m not sure.
As I understand it, miRNA is a short strand of RNA that binds to messenger RNA at some appropriate site. This interferes with the production of the proteain associated with that messenger RNA.
Isn’t this what siRNA does too? or is siRNA something different…or does… wait…:smack: dammit.
Its complicated because many people do use the terms interchangeably. Its confusing because miRNAs, after processing, form siRNAs
microRNAs (miRNAs) are genomically encoded and are now recognized as a major mechanism for regulating gene expression. They are encoded as long pre-miRNA genes and are modified post-transciptionally to form the interfering RNAs. They often do not base-pair perfectly during hairpin formation and can modify the expression of multiple genes that share sequence homology.
siRNAs can be genomically encoded or can come from exogenous RNA (viral genomes, artificially synthesized etc). They base-pair perfectly and typically regulate a single specific sequence.
I don’t pretend to have great understanding of noncoding RNAs, but best as I can tell, miRNAs (or rather, pre-miRNAs) are bigger (75 nt vs 21 nt), are further back in the processing pathway, and are eventually processed by Dicer and similar enzymes into siRNA, which is the actual effector. The nomenclature isn’t very consistent.
Part of the inconsistency seems to be that miRNA is described purely in terms of size, while siRNA has a functional component in its description.
So if I have a synthesized 21 mer RNA molecule, it is more correctly called an siRNA than miRNA because it is that short? Also because (presumably) the sequence I have of this 21 mer makes it specifically functional for a single gene.
I would say so, yes. siRNA implies a specific function, while miRNAs can do all sorts of things. Is another way of looking at it. Then there are trans-acting siRNAs, or ta-siRNAs, which are a weird mixture of the two.
To expand a bit on miRNA functions, there’s a lot they can do to regulate target transcripts. Some simply form hairpins or double stranded RNA with their target transcript, and are thus recognized by Dicer and chopped up into siRNAs. That sets off the RNA interference pathway, silencing the target transcript. Now, other miRNAs will also bind to target transcripts and regulate them, independent of Dicer activity. For example, some miRNAs will block translation by binding to 5’ UTRs, with some sort of secondary structure that prevents Dicer activity. I also recall that there are other miRNAs that can activate translation by “melting” inhibitory secondary structures on a particular transcript.
But if you just have a 21-mer that synthesized to knock down some gene of interest, it’s a siRNA.
My eyes usually glaze over a bit whenever I go to a talk describing a new family of small RNAs, which are similar to all of the other small RNAs but distinct in some way that’s important to the investigator…
Oh yeah. Over the last fifteen years or so there’s been a huge boom in discoveries of all sorts of odd little RNAs. Wiki’s list will give you a good flavor of all the sorts of RNAs that we know of. It’s currently a pretty hot research topic; many groups are hard at work discovering and classifying new types of RNAs, as well as figuring out the underlying mechanisms.
And, for the record, the “central dogma” of molecular biology (DNA -> RNA -> protein) is stuffed with exceptions these days. There are all sorts feedback and regulatory mechanisms at every conceivable point, with small RNAs involved much of the time.
And we sit quietly, on the fringes, sadly watching any chance of the interested lay audience understanding the conversation slip quietly into the vast darkness.
For a while there, I was working on a project where we were pretty sure we were about to discover a whole new category of very important small RNAs. Couldn’t get any damn thing to work, though. I still think we were on the right track, but it must be doing something so weird or bound to something so tightly that standard protocols for extraction and RT-PCR and whatnot don’t work very well.
I moved on. Maybe I’ll revisit it one of these days.