PXD027966

PXD027966 is an original dataset announced via ProteomeXchange.

Title	Chromatin-associated RNA degradation contributes to silencing of Polycomb target genes
Description	Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2) are histone-modifying and -binding complexes that mediate the formation of facultative heterochromatin and are required for silencing of developmental genes and maintenance of cell fate. Multiple pathways of RNA decay work together to establish and maintain heterochromatin in fission yeast, including a recently identified role for a conserved RNA degradation complex called the rixosome or RIX1 complex. Whether RNA degradation also plays a role in the stability of mammalian heterochromatin remains unknown. Here we show that the rixosome contributes to silencing of many Polycomb targets in human cells. The rixosome associates with human PRC complexes and is enriched at promoters of Polycomb target genes. Importantly, depletion of either the rixosome or Polycomb results in accumulation of paused and elongating RNA polymerase at Polycomb-target genes. We identify point mutations in the RING1B subunit of PRC1 that disrupt the interaction between PRC1 and the rixosome and result in diminished silencing, suggesting that direct recruitment of the rixosome to chromatin is required for silencing. Finally, we show that the RNA kinase activity of the rixosome and the XRN2 exoribonuclease, which degrades RNAs with 5’ mono-phosphate groups generated by the rixosome, are required for silencing. Our findings suggest that rixosome-mediated degradation of nascent RNA is conserved from fission yeast to human, although in human cells the rixosome degrades RNA in facultative rather than constitutive heterochromatin.
HostingRepository	PRIDE
AnnounceDate	2022-01-27
AnnouncementXML	Submission_2022-05-06_09:02:07.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-17 04:05:12	ID requested
1	2022-01-19 10:16:14	announced
2	2022-01-27 08:56:19	announced	2022-01-27: Updated project metadata.
⏵ 3	2022-05-06 09:02:08	announced	2022-01-27: Updated project metadata. 2022-05-06: Updated publication reference for PubMed record(s): 35355014.

Zhou H, Stein CB, Shafiq TA, Shipkovenska G, Kalocsay M, Paulo JA, Zhang J, Luo Z, Gygi SP, Adelman K, Moazed D, Rixosomal RNA degradation contributes to silencing of Polycomb target genes. Nature, 604(7904):167-174(2022) [pubmed]

submitter keyword: PRC2, polycomb, PRC1, RIX1,RNA degradation, rixosome

Danesh Moazed
contact affiliation	Cell Biology Harvard Medical School Boston, MA 02115
contact email	danesh_moazed@hms.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027966
     1. Label: PRIDE project
     2. Name: Chromatin-associated RNA degradation contributes to silencing of Polycomb target genes