RT Journal Article
T1 Human THO-Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability.
A1 Salas-Armenteros, Irene
A1 Pérez-Calero, Carmen
A1 Bayona-Feliu, Aleix
A1 Tumini, Emanuela
A1 Luna, Rosa
A1 Aguilera, Andrés
K1 DNA–RNA hybrids
K1 Sin3A deacetylase
K1 THO/TREX
K1 genome instability
K1 histone acetylation
AB R-loops, formed by co-transcriptional DNA-RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R-loop accumulation centers on the conserved THO/TREX complex, an RNA-binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R-loops, we searched for new THO-interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co-transcriptional R-loops, DNA damage, and replication impairment. Functional analyses show that histone hypo-acetylation prevents accumulation of harmful R-loops and RNA-mediated genomic instability. Diminished histone deacetylase activity in THO- and Sin3A-depleted cell lines correlates with increased R-loop formation, genomic instability, and replication fork stalling. Our study thus uncovers physical and functional crosstalk between RNA-binding factors and chromatin modifiers with a major role in preventing R-loop formation and RNA-mediated genome instability.
YR 2017
FD 2017-10-26
LK http://hdl.handle.net/10668/11735
UL http://hdl.handle.net/10668/11735
LA en
DS RISalud
RD Apr 5, 2025