Moazed lab reveals a co-transcriptional gene repression mechanism via nascent RNA degradation

Rixosome-mediated Nascent RNA degradation and transcriptional repression

In a paper published in Nature, the Moazed lab describes a novel mechanism of gene silencing in mammalian cells, which involves the degradation of nascent RNAs by a seven-subunit protein complex called the rixosome. The rixosome is recruited to promoter regions in facultative heterochromatin by the Polycomb complex PRC1. The endoribonuclease LAS1L subunit of the rixosome then cleaves nascent RNA that is synthesized by RNA polymerase II. Another subunit of the rixosome, NOL9, phosphorylates the cleaved RNA so that it becomes a substrate for the XRN2 exoribonuclease. XRN2 mediates rapid and full degradation of nascent RNA and release of RNA Pol II. Rixosomal RNA degradation may provide an additional layer of repression that ensures full silencing of Polycomb target genes.