LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay

In fission yeast and plants, RNA-processing and degradation contribute to heterochromatin silencing, alongside conserved pathways of transcriptional repression. It was unknown if similar pathways exist in metazoans. Here we describe a pathway of silencing in C. elegans somatic cells, in which the highly conserved RNA binding complex LSM2-8 contributes selectively to the repression of heterochromatic reporters and endogenous genes bearing the Polycomb mark, histone H3K27me3. It acts by degrading selected transcripts through the XRN-2 exoribonuclease. Disruption of the LSM2-8 pathway leads to mRNA stabilization. Unlike previously described pathways of heterochromatic RNA degradation, LSM2-8-mediated RNA degradation does not require nor deposit H3K9 methylation. Rather, loss of this pathway coincides with a localized reduction in H3K27me3 at lsm-8-sensitive loci. Thus, we have uncovered a mechanism of RNA degradation that selectively contributes to the silencing of a subset of H3K27me3-marked genes, revealing a previously unrecognized layer of post-transcriptional control in metazoan heterochromatin.