The exosome degrades chromatin-associated RNAs genome-wide and maintains chromatin homeostasis

• Chromatin-associated RNAs (caRNAs) modulate chromatin organization and function. The RNAexosome degrades different types of nuclear transcripts, but its role in chromatin has not beenaddressed. Here we have used Drosophila melanogaster S2 cells as a model system to identify therepertoire of caRNAs and establish the role of the exosome in their regulation. We have analyzed bothunique and repetitive sequences, and combining RNA-seq and ATAC-seq we show that thesimultaneous depletion of the exosome catalytic subunits RRP6 and DIS3 not only affects caRNAlevels but also changes the local chromatin accessibility at specific loci. We have identified a group ofexosome-sensitive genes that are involved in developmental regulation and are characterized by abalanced chromatin state in which Polycomb and Trithorax factors coexist. Our results reveal that RNAdegradation by the exosome is an important mechanism for the homeostasis of such balancedchromatin states. Given that eukaryotic genomes are repetitive to a large extent, we have also analyzed repetitive caRNAs (rep-caRNAs) and we show that the exosome is needed to control repcaRNAlevels and to maintain the degree of chromatin packaging in repetitive genomic regions. Thisrole is particularly relevant in the pericentromeric regions where the exosome is required to silenceLTR elements and maintain centromere organization.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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