Non-coding RNAs and chromatin modification

RNA molecules that do not encode protein account for a surprisingly large proportion of transcription in complex organisms including humans. It now seems that many of these non-coding (nc)RNAs have regulatory functions, representing a previously hidden layer of complexity in genome regulation. Our main interest is in the role of ncRNAs in epigenetic regulation of gene expression via chromatin modification.

A growing list of non-coding RNAs are implicated in the chromatin modifications, including DNA methylation and histone modification, that modulate gene expression during development. Examples include long non-coding RNAs such as Xist and AIR involved in X-inactivation and imprinting in mammals, and short PIWI-interacting (pi)RNAs involved in silencing transposons in the mammalian germline. Defects in RNA-directed chromatin modification have been implicated in a number of diseases including cancers; however, the molecular mechanisms underlying this process remain poorly defined.

Our goal is to better understand the role of non-coding RNAs in chromatin-dependent gene regulation. In particular we are interested in chromatin-related functions of the RNA interference (RNAi) pathway, a conserved gene silencing mechanism mediated by small non-coding RNAs. Our current research focuses on understanding how small RNAs direct the chromatin modifications associated with heterochromatin assembly in the fission yeast Schizosaccharomyces pombe-this single-celled eukaryote is an ideal genetic model because despite its relative simplicity, it shares both RNAi and chromatin components with humans. We employ a combination of genetic, molecular and biochemical approaches to investigate how non-coding RNAs direct chromatin modification, how this process is regulated, and what biological functions it serves.

• Lejeune E., Bayne E.H., Allshire R.C. (2011) On the Connection between RNAi and Heterochromatin at Centromeres. Cold Spring Harb Symp Quant Biol. published online Feb 2.
• Bayne, E.H., White, S.A., Kagansky, A., Bijos, D.A., Sanchez-Pulido, L., Hoe, K-L., Kim, D-U., Park, H-O., Ponting, C.P., Rappsilber, J., and Allshire, R.C.(2010) Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity. Cell 140: 666-677
• Djupedal, I., Kos-Braun, I.C., Mosher, R.A., Söderholm, N., Simmer, F., Hardcastle, T.J., Fender, A., Heidrich, N., Kagansky, A., Bayne, E.H., Wagner, E.G.H., Baulcombe, D.C., Allshire, R.C., and Ekwall, K. (2009) Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA. EMBO Journal 28: 3832-3844
• Bayne, E.H., Portoso M., Kagansky A., Kos-Braun I.C., Urano T., Ekwall K., Alves F., Rappsilber J., Allshire R.C. (2008) Splicing factors facilitate RNAi-directed silencing in fission yeast. Science 322: 602-606
• Bayne, E.H., White S.A., Allshire R.C. (2007) DegrAAAded into silence. Cell 129: 651-653
• Bayne, E.H. and Allshire, R.C. (2005) RNA-directed transcriptional gene silencing in mammals. Trends in Genetics 21: 370-373
• Bayne, E.H., Rakitina, D.V., Morozov, S.Y., and Baulcombe, D.C. (2005) Cell-to-cell movement of Potato Potexvirus X is dependent on suppression of RNA silencing. Plant Journal 44: 471-482