Small RNA shows its power

Until recently, gene control of cell structure and physiology was summed up as DNA makes RNA that in turn makes proteins. However, the world of small RNAs has overturned this. Basically, miRNAs downregulate gene expression by attaching themselves to the messenger RNAs (mRNAs), preventing their translation into proteins.

However, this seems to be yet another oversimplification of gene control and the 'Argonaute-associated factors required for translational repression in plant RNA silencing' (ASTRIR) project has researched different mechanisms of gene transcription control in thale cress, Arabidopsis thaliana. Their focus lay on ARGONAUTE 1 (AGO1), part of the RNA-induced silencing complexes (RISCs).

AGO1 incorporates an enzyme that slices mRNA targets, an activity that is prevented on mismatching. Such mismatches promote in turn other control mechanisms including mRNA decay. Contrary to many research findings, the ASTRIR lab has investigated how A. thaliana can concurrently avoid slicing during inhibition of transcription.

One possibility is the action of other proteins that can associate with AGO1. One, eIF4a1, changed the mode of action of AGO1 and appears to programme the RISC so it indulges in a non-slicing mode of action to go the translational repression route. Interestingly, one eIF4a1 mutant has increased resistance when infected with a major pathogen, the tobacco rattle virus.

Further investigation on the molecular scale involved isolation of the entire translational machinery. Four different silencing factors from the AGO family were identified that associate with groups of ribosomes (polysomes). An interesting result is that only part of the total miRNAs can be isolated with the machinery, inferring that only specific members are involved with translational repression.

Deep silencing analysis has revealed a large number of small interfering RNAs connected with polysomes, although their role at present is unclear. However, the researchers speculate that further research into these molecules as effectors of translational repression may yield valuable results.

Using novel research approaches, ASTRIR results have shed light on the mechanisms of small RNA gene regulation across the board from bacteria to all higher organisms. In particular, the role of these tiny but highly significant molecules in antiviral defence may well offer a basis for new tools and therapeutic solutions.