Human Senataxin Resolves RNA/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination

327Citations
Citations of this article
403Readers
Mendeley users who have this article in their library.

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. © 2011 Elsevier Inc.

Cite

CITATION STYLE

APA

Skourti-Stathaki, K., Proudfoot, N. J., & Gromak, N. (2011). Human Senataxin Resolves RNA/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination. Molecular Cell, 42(6), 794–805. https://doi.org/10.1016/j.molcel.2011.04.026

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free