SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability.
Animals
Cell Line, Tumor
DNA
/ metabolism
DNA Replication
DNA-Binding Proteins
Homologous Recombination
Humans
Mice
Nuclear Matrix-Associated Proteins
/ metabolism
Nucleic Acid Hybridization
Octamer Transcription Factors
/ metabolism
PTB-Associated Splicing Factor
/ metabolism
RNA
/ metabolism
RNA, Untranslated
RNA-Binding Proteins
/ metabolism
Telomere
/ metabolism
Telomere Homeostasis
Telomere-Binding Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
29
01
2018
accepted:
21
01
2019
entrez:
3
3
2019
pubmed:
3
3
2019
medline:
5
4
2019
Statut:
epublish
Résumé
In vertebrates, the telomere repeat containing long, non-coding RNA TERRA is prone to form RNA:DNA hybrids at telomeres. This results in the formation of R-loop structures, replication stress and telomere instability, but also contributes to alternative lengthening of telomeres (ALT). Here, we identify the TERRA binding proteins NONO and SFPQ as novel regulators of RNA:DNA hybrid related telomere instability. NONO and SFPQ locate at telomeres and have a common role in suppressing RNA:DNA hybrids and replication defects at telomeres. NONO and SFPQ act as heterodimers to suppress fragility and homologous recombination at telomeres, respectively. Combining increased telomere fragility with unleashing telomere recombination upon NONO/SFPQ loss of function causes massive recombination events, involving 35% of telomeres in ALT cells. Our data identify the RNA binding proteins SFPQ and NONO as novel regulators at telomeres that collaborate to ensure telomere integrity by suppressing telomere fragility and homologous recombination triggered by RNA:DNA hybrids.
Identifiants
pubmed: 30824709
doi: 10.1038/s41467-019-08863-1
pii: 10.1038/s41467-019-08863-1
pmc: PMC6397292
doi:
Substances chimiques
DNA-Binding Proteins
0
NONO protein, human
0
Nuclear Matrix-Associated Proteins
0
Octamer Transcription Factors
0
PTB-Associated Splicing Factor
0
RNA, Untranslated
0
RNA-Binding Proteins
0
Telomere-Binding Proteins
0
RNA
63231-63-0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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