Human Senataxin Resolves RNA/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination
By Konstantina Skourti-Stathaki, N. Proudfoot, N. Gromak. Molecules and Cells, 2011
784 citations recorded by the source corpus.
Summary We present a molecular dissection of pause site-dependent transcriptional termination for mammalian RNA polymerase II (Pol II)-transcribed genes. We show that nascent transcripts form RNA/DNA hybrid structures (R-loops) behind elongating Pol II and are especially prevalent over G-rich pause sites positioned downstream of gene poly(A) signals. Senataxin, a helicase protein associated with AOA2/ALS4 neurodegenerative disorders, acts to resolve these R-loop structures and by so doing allows access of the 5′–3′ exonuclease Xrn2 at 3′ cleavage poly(A) sites. This affords 3′ transcript degradation and consequent Pol II termination. In effect, R-loops formed over G-rich pause sites, followed by their resolution by senataxin, are key steps in the termination process.
Subfields: Molecular Biology, Plant Science
View Paper: https://www.semanticscholar.org/paper/1e73bd01e8e6ff9bd243bde86a7b7df54829546f
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Citations in the corpus
- R loops: from transcription byproducts to threats to genome stability. (2012, background): “It has been proposed that R loops may be critical for RNAPII to pause downstream of the poly(A) site and that Senataxin may unwind the RNA:DNA hybrids (Skourti-Stathaki et al., 2011).”
- R-loops as cellular regulators and genomic threats (2019, background): “Consistent with this idea, loss of SETX, DHX9 or XRN2 results in R-loop accumulation and defective termination (Cristini et al., 2018; Morales et al., 2016; Skourti-Stathaki et al., 2011).”
- Recent advances in RNA structurome (2022, background): “G4s in mRNAs are involved in multiple functions, including transcription termination (Skourti-Stathaki et al., 2011), alternative splicing (Didiot et al., 2008), polyadenylation (Beaudoin and Perreault, 2013), mRNA localization and stability (Ishiguro et al., 2016; Zalfa et al., 2007), as well as…”