Nuclear action of miRNAs

03-DYNA-F-19: Nuclear action of miRNAs

Abstract:

Double stranded RNA (dsRNA) is potent inducer of gene silencing. The mechanism by which these molecules induce silencing is evolutionary conserved, and represents a very powerful and specific way of gene activity control. One of the intermediates of this silencing process is a short RNA(Srna) molecule that has been named short interfering RNA (siRNA) or micro RNA (miRNA). These molecules act as guides for either an RNA degradation enzyme that is active in the cytosol or a complex that targets translation inhibition. In addition to these cytosolic events, nuclear effects of dsRNA have also been observed. In plants, dsRNA leads to methylation of homologous DNA sequences, and induces transcriptional silencing when promoter DNA is targeted. In yeast, dsRNA mediated processes have been implicated in centromere function. In animals, evidence for such nuclear effects has been obtained as well. For example, phenotypes of C. elegans mutants defective in RNAi suggest an impaired centromere function, and partially overlap with phenotypes associated with defects in the maintenance of silent chromatin states. In this research proposal we aim at a better understanding of the nuclear effects of dsRNA. We will do this by analyzing nuclear dsRNA processing, by identifying nuclear sRNA, by analyzing proteins associating with the nuclear sRNA and by analyzing the effects of nuclear sRNA on chromatin modifications and transcriptional activity.

Project Leader:

Dr. René F. Ketting
Hubrecht Laboratory
Netherlands Institute for Developmental Biology
3584 CT Utrecht Netherlands
Phone:+31 30 2121 963
Fax:+31 30 251 6554
Email

Principal Investigators:

Marjori Matzke, Austrian Academy of Sciences, Vienna, AT