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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Format: | Journal article |
Language: | English |
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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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format | Journal article |
id | oxford-uuid:64f2b640-f129-4b53-b99a-325e61a1e78e |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T23:09:24Z |
publishDate | 2011 |
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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 |
work_keys_str_mv | AT skourtistathakik humansenataxinresolvesrnadnahybridsformedattranscriptionalpausesitestopromotexrn2dependenttermination AT proudfootn humansenataxinresolvesrnadnahybridsformedattranscriptionalpausesitestopromotexrn2dependenttermination AT gromakn humansenataxinresolvesrnadnahybridsformedattranscriptionalpausesitestopromotexrn2dependenttermination |