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

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 po...

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Main Authors: Skourti-Stathaki, K, Proudfoot, N, Gromak, N
Format: Journal article
Language:English
Published: 2011
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author Skourti-Stathaki, K
Proudfoot, N
Gromak, N
author_facet Skourti-Stathaki, K
Proudfoot, N
Gromak, N
author_sort Skourti-Stathaki, K
collection OXFORD
description 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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spelling oxford-uuid:64f2b640-f129-4b53-b99a-325e61a1e78e2022-03-26T18:22:14ZHuman senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:64f2b640-f129-4b53-b99a-325e61a1e78eEnglishSymplectic Elements at Oxford2011Skourti-Stathaki, KProudfoot, NGromak, NWe 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.
spellingShingle Skourti-Stathaki, K
Proudfoot, N
Gromak, N
Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
title Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
title_full Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
title_fullStr Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
title_full_unstemmed Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
title_short Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
title_sort human senataxin resolves rna dna hybrids formed at transcriptional pause sites to promote xrn2 dependent termination
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AT proudfootn humansenataxinresolvesrnadnahybridsformedattranscriptionalpausesitestopromotexrn2dependenttermination
AT gromakn humansenataxinresolvesrnadnahybridsformedattranscriptionalpausesitestopromotexrn2dependenttermination