RNA turns genes off!

Right, turning genes off is just one of the things that RNA is very good at doing. This process is called RNA-interference (RNAi) because the small RNA interferes with the gene’s mRNA moving from the transcription to translation processes (see blog 1 for a refresher on this). Today I will explain one part of RNAi which is how microRNAs (miRNAs) kind of work.

Small RNAs are transcribed that fold back upon themselves in what is called a hairpin loop structure so you have a double stranded RNA with two sides that are complementary. The pairing generally works as follows: A’s bind to U’s, The C’s bind to G’s, but with RNA the G’s can bind to C and U, and U can bind to A and G to give a bit more flexibility.

Double-stranded RNAs are targeted in the cell by the DICER protein and chopped into 20 nucleotide long fragments. One of the fragments (the miRNA) is picked up by the RISC system (RNA-induced silencing complex) which then goes looking for the mRNA with a sequence matching the small miRNA sequence. When this gene’s mRNA is found the miRNA binds to the mRNA and another protein called ARGONAUTE in the RISC chops the mRNA. As a consequence the mRNA does not move to translation and the gene is ‘silenced’. Essentially the RISC uses the miRNA as the signal to find its target gene.This is only one way in that miRNAs silence genes and there are many variations on this theme. RNAi systems in general are found throughout eukaryotes (cells with a nucleus) and a similar system has been found in prokaryotes (something for a later blog). An exception is the yeast Saccharomyces cerevisiae (baker’s yeast) which has lost many of the RNAi proteins. How S. cerevisiae turns its genes off without using the standard RNA-based system is the subject of much research.


Unraveling the Mysteries of Small RNAsDianne S. Schwarz, Science Online feature http://www.sciencemag.org/feature/data/prizes/ge/2006/schwarz.dtl 
 

RNAi is used in the cell for other gene regulation processes including epigenetics and virus protection. I will expand on each of these in further blogs.


Matzke MA, Matzke AJM (2004) Planting the Seeds of a New Paradigm. PLoS Biol 2(5): e133.

Early Examples of Gene Silencing in Transgenic Plants – what happens when you silence genes in petunias