Life Sciences Research for Lifelong Health

Non-coding RNAs in gene regulation

Non-protein coding RNAs can regulate gene expression in many different ways, and multiple mechanisms for gene repression through modification of chromatin structure have been demonstrated. For example, we have shown that a non-coding RNA in the cluster of yeast genes required for galactose metabolism fine-tunes gene expression in complex environments. We are beginning to use systems biology approaches to study how gene expression responds to environmental change, and to what extent this is coordinated by non-coding RNA.

One mechanism by which non-protein coding RNAs might influence gene expression is through the initiation of RNA interference (RNAi) responses, however evidence for this process occurring in vivo has been surprisingly rare. We have recently demonstrated that such regulation can indeed occur but is highly sensitive to gene copy number, being principally active in high-copy genomic regions. This provides one mechanism by which changes in gene copy number can have major effects on gene expression.

RNAi figure
Proposed mechanism for selectivity of RNAi towards high copy loci. Multi-copy loci can produce a high local concentration of sense and antisense RNA in the vicinity of the transcription site, driving double stranded RNA formation

This process provides a solution to a very old question: it is known that most organisms silence high-copy genomic regions, but how does the cell ‘count’ copy number? Our research has shown that as long as these regions are transcribed at a low level, the level of double-stranded RNA production is highly indicative of copy number, which can be used to direct silencing machinery. This provides a compelling reason for the recent observation that eukaryotic genomes are pervasively transcribed into low abundance non-coding RNA of unknown function. We suggest that pervasive transcription provides a mechanism to count copy number and selectively silence new multi-copy sequences, allowing cells to identify and suppress new transposons amplifying with the genome.

pervasive figure