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

ABSTRACT: The LSM2-8 complex specifically targets nuclear RNAs generated from loci bearing histone H3K27me3 for degradation through the exonuclease XRN-2 In fission yeast and plants RNA-processing pathways including co-transcriptional degradation of nuclear mRNAs contributes to heterochromatic gene silencing additionally to the well-known transcriptional repression, but it was not knownunclear if this extra level of regulation also to occur in metazoans. Here we report the discovery of a related pathway in somatic cells of the flatworm C. elegans. The highly conserved, RNA binding LSM2-8 complex is shown to silence selectively heterochromatic reporters and endogenous genes bearing the Polycomb mark H2K27me3. LSM2-8-mediated silencing is independent of H3K9me2/me3 but depends on mes-2, the Polycomb-like histone methyl transferase. LSM2-8-mediated silencing is detectable from early embryonic stages through adulthood. The LSM2-8 complex works cooperatively with XRN-2, a 5’-3’ exonuclease, and disruption of the pathway leads to stabilized targeted mRNAs. Developmental defects and premature death were observed in worms lacking LSM-8, and levels of H3K27me3 dropped slightly at Pc-targeted loci. LSM2-8-mediated silencing of H3K27me3-bound regions defines a new mechanism of selective heterochromatin gene silencing not previously shown for higher eukaryotes.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE133356 | GEO | 2020/02/12

REPOSITORIES: GEO

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

Project description:The LSM2-8 complex specifically targets nuclear RNAs generated from loci bearing histone H3K27me3 for degradation through the exonuclease XRN-2 In fission yeast and plants RNA-processing pathways including co-transcriptional degradation of nuclear mRNAs contributes to heterochromatic gene silencing additionally to the well-known transcriptional repression, but it was not knownunclear if this extra level of regulation also to occur in metazoans. Here we report the discovery of a related pathway in somatic cells of the flatworm C. elegans. The highly conserved, RNA binding LSM2-8 complex is shown to silence selectively heterochromatic reporters and endogenous genes bearing the Polycomb mark H2K27me3. LSM2-8-mediated silencing is independent of H3K9me2/me3 but depends on mes-2, the Polycomb-like histone methyl transferase. LSM2-8-mediated silencing is detectable from early embryonic stages through adulthood. The LSM2-8 complex works cooperatively with XRN-2, a 5’-3’ exonuclease, and disruption of the pathway leads to stabilized targeted mRNAs. Developmental defects and premature death were observed in worms lacking LSM-8, and levels of H3K27me3 dropped slightly at Pc-targeted loci. LSM2-8-mediated silencing of H3K27me3-bound regions defines a new mechanism of selective heterochromatin gene silencing not previously shown for higher eukaryotes.

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