Jun 28, 2011

Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination

Molecular Cell
Konstantina Skourti-StathakiNatalia Gromak

Abstract

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.

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  • Citations290

Citations

Mentioned in this Paper

Real-Time Polymerase Chain Reaction
RNA Polymerase II
DNA Helicase Activity
Transcriptional Regulation
Nucleosomes
Carboxy-Terminal Amino Acid
Ribonuclease H1
DNA Repair
Actins
Western Blotting

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