Cell-Cycle Modulation of Transcription Termination Factor Sen1

TY - JOUR

T1 - Cell-Cycle Modulation of Transcription Termination Factor Sen1

AU - Mischo, Hannah E.

AU - Chun, Yujin

AU - Harlen, Kevin M.

AU - Smalec, Brendan M.

AU - Dhir, Somdutta

AU - Churchman, L. Stirling

AU - Buratowski, Stephen

PY - 2018/4/19

Y1 - 2018/4/19

N2 - 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. Transcription termination of noncoding RNAs by the Nrd1-Nab3-Sen1 (NNS) complex is affected by Sen1 protein levels. Controlled Sen1 degradation during the G1 phase of the cell cycle reduces NNS termination efficiency. In contrast, increased Sen1 levels lead to overactive noncoding RNA termination and reduced cell viability.

AB - 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. Transcription termination of noncoding RNAs by the Nrd1-Nab3-Sen1 (NNS) complex is affected by Sen1 protein levels. Controlled Sen1 degradation during the G1 phase of the cell cycle reduces NNS termination efficiency. In contrast, increased Sen1 levels lead to overactive noncoding RNA termination and reduced cell viability.

KW - cell cycle

KW - NNS

KW - non-coding RNA

KW - Nrd1-Nab3-Sen1

KW - Sen1

KW - transcription termination

KW - ubiquitin-proteasome system

UR - http://www.scopus.com/inward/record.url?scp=85045247509&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2018.03.010

DO - 10.1016/j.molcel.2018.03.010

M3 - Article

C2 - 29656924

AN - SCOPUS:85045247509

SN - 1097-2765

VL - 70

SP - 312

EP - 326

JO - MOLECULAR CELL

JF - MOLECULAR CELL

IS - 2

M1 - e7

ER -