Broad Institute, Cambridge, Massachusetts
A biologist looks at new functions for non-coding RNAs.
The increasing study of small and large RNA molecules that do not encode protein — non-coding RNAs — is widening our view of their relevance, and of their roles in important developmental mechanisms such as gene silencing and X-chromosome inactivation. Nevertheless, our knowledge covers only a fraction of the non-coding transcripts produced from the mammalian genome.
Much of the non-coding RNA transcribed is associated with protein-coding genes: for example, the transcripts that are complementary or ‘antisense’ to the gene sequence. These can be created by ‘bidirectional’ transcription from either DNA strand. Kevin Morris of the Scripps Research Institute in La Jolla, California, and his colleagues have now shed light on the function of this type of transcription (K. V. Morris et al. PLoS Genet. 4, e1000258; 2008).
They focused on the gene encoding the tumour suppressor p21, transcription of which must be finely tuned, and show that an endogenous antisense transcript of p21 controls the amount of p21 mRNA made by silencing its promoter. This transcriptional suppression is dependent on Argonaute-1, a protein implicated in RNA-mediated gene silencing. Suppression correlates with bidirectional transcription within p21’s promoter.
This observation is not limited to p21: a similar regulatory mechanism controls gene expression of the protein E-cadherin, suggesting that this balancing of sense and antisense transcription might be a common mechanism of transcriptional regulation.
The next challenge is to understand how RNAs can induce transcriptional gene silencing; information that will probably reveal just how much power RNA wields in the control of gene expression.