Cell-cycle modulation of transcription termination factor Sen1

Many non-coding transcripts (ncRNA) generated by RNA polymerase II in S. cerevisiae are terminated by the Nrd1-Nab3-Sen1 complex. However, Sen1 helicase levels are surprisingly low compared with Nrd1 and Nab3, raising questions regarding how ncRNA can be terminated in an efficient and timely manner....

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Main Authors: Mischo, H, Chun, Y, Harlen, K, Smalec, B, Dhir, S, Churchman, L, Buratowski, S
Format: Journal article
Published: Cell Press 2018
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author Mischo, H
Chun, Y
Harlen, K
Smalec, B
Dhir, S
Churchman, L
Buratowski, S
author_facet Mischo, H
Chun, Y
Harlen, K
Smalec, B
Dhir, S
Churchman, L
Buratowski, S
author_sort Mischo, H
collection OXFORD
description Many non-coding transcripts (ncRNA) generated by RNA polymerase II in S. cerevisiae are terminated by the Nrd1-Nab3-Sen1 complex. However, Sen1 helicase levels are surprisingly low compared with Nrd1 and Nab3, raising questions regarding how ncRNA can be terminated in an efficient and timely manner. We show that Sen1 levels increase during the S and G2 phases of the cell cycle, leading to increased termination activity of NNS. Overexpression of Sen1 or failure to modulate its abundance by ubiquitin-proteasome-mediated degradation greatly decreases cell fitness. Sen1 toxicity is suppressed by mutations in other termination factors, and NET-seq analysis shows that its overexpression leads to a decrease in ncRNA production and altered mRNA termination. We conclude that Sen1 levels are carefully regulated to prevent aberrant termination. We suggest that ncRNA levels and coding gene transcription termination are modulated by Sen1 to fulfill critical cell cycle-specific functions.
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spelling oxford-uuid:9eb4940f-ef08-47d9-a677-33155b5015ce2022-03-27T00:52:05ZCell-cycle modulation of transcription termination factor Sen1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9eb4940f-ef08-47d9-a677-33155b5015ceSymplectic Elements at OxfordCell Press2018Mischo, HChun, YHarlen, KSmalec, BDhir, SChurchman, LBuratowski, SMany non-coding transcripts (ncRNA) generated by RNA polymerase II in S. cerevisiae are terminated by the Nrd1-Nab3-Sen1 complex. However, Sen1 helicase levels are surprisingly low compared with Nrd1 and Nab3, raising questions regarding how ncRNA can be terminated in an efficient and timely manner. We show that Sen1 levels increase during the S and G2 phases of the cell cycle, leading to increased termination activity of NNS. Overexpression of Sen1 or failure to modulate its abundance by ubiquitin-proteasome-mediated degradation greatly decreases cell fitness. Sen1 toxicity is suppressed by mutations in other termination factors, and NET-seq analysis shows that its overexpression leads to a decrease in ncRNA production and altered mRNA termination. We conclude that Sen1 levels are carefully regulated to prevent aberrant termination. We suggest that ncRNA levels and coding gene transcription termination are modulated by Sen1 to fulfill critical cell cycle-specific functions.
spellingShingle Mischo, H
Chun, Y
Harlen, K
Smalec, B
Dhir, S
Churchman, L
Buratowski, S
Cell-cycle modulation of transcription termination factor Sen1
title Cell-cycle modulation of transcription termination factor Sen1
title_full Cell-cycle modulation of transcription termination factor Sen1
title_fullStr Cell-cycle modulation of transcription termination factor Sen1
title_full_unstemmed Cell-cycle modulation of transcription termination factor Sen1
title_short Cell-cycle modulation of transcription termination factor Sen1
title_sort cell cycle modulation of transcription termination factor sen1
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AT chuny cellcyclemodulationoftranscriptionterminationfactorsen1
AT harlenk cellcyclemodulationoftranscriptionterminationfactorsen1
AT smalecb cellcyclemodulationoftranscriptionterminationfactorsen1
AT dhirs cellcyclemodulationoftranscriptionterminationfactorsen1
AT churchmanl cellcyclemodulationoftranscriptionterminationfactorsen1
AT buratowskis cellcyclemodulationoftranscriptionterminationfactorsen1