RNA turnover and chromatin-dependent gene silencing

Marc Bühler

Over the last few years, there has been a convergence of two seemingly disparate fields of study: chromatin-dependent gene silencing and RNA turnover. In contrast to RNA turnover mechanisms that operate on a truly posttranscriptional level, we are at the beginning of studies leading the way toward a model in which RNA turnover mechanisms are also involved in chromatin-dependent gene regulation. In particular, data from a variety of organisms have shown that the assembly of silent chromatin coincides with the presence or absence of non-protein-coding RNAs (ncRNAs). These range from long ncRNAs that have been classically implicated in the regulation of dosage compensation and genomic imprinting to small ncRNAs which are involved in heterochromatin assembly via the RNA interference (RNAi) pathway. This raises the question of how common ncRNAs are used to control gene expression at the level of chromatin. It is known at least, that they are present, as recent findings indicate that transcription of eukaryotic genomes is much more widespread than previously anticipated. However, the existence of a ncRNA does not prove its biological significance. Thus, a future challenge will be to distinguish the ncRNAs that are in some way meaningful to the organism from those that arise from the imperfect fidelity of the transcription machinery. Finally, no matter whether functional or not, RNAs transcribed from supposedly silent chromatin seem to be processed rapidly. Recent data from both fission and budding yeast suggest that chromatin-dependent gene silencing is achieved, at least in part, through RNA turnover mechanisms that use components of the RNAi pathway as well as polyadenylation-dependent RNA decay. Hence, silent chromatin is not only controlled transcriptionally, but also on co- and posttranscriptional levels.