SCAF4 and SCAF8, mRNA Anti-Terminator Proteins
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SCAF4 and SCAF8, mRNA Anti-Terminator Proteins. / Gregersen, Lea H.; Mitter, Richard; Ugalde, Alejandro P; Nojima, Takayuki; Proudfoot, Nicholas J; Agami, Reuven; Stewart, Aengus; Svejstrup, Jesper Q.
I: Cell, Bind 177, Nr. 7, 2019, s. 1797-1813.e18.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - SCAF4 and SCAF8, mRNA Anti-Terminator Proteins
AU - Gregersen, Lea H.
AU - Mitter, Richard
AU - Ugalde, Alejandro P
AU - Nojima, Takayuki
AU - Proudfoot, Nicholas J
AU - Agami, Reuven
AU - Stewart, Aengus
AU - Svejstrup, Jesper Q
N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Accurate regulation of mRNA termination is required for correct gene expression. Here, we describe a role for SCAF4 and SCAF8 as anti-terminators, suppressing the use of early, alternative polyadenylation (polyA) sites. The SCAF4/8 proteins bind the hyper-phosphorylated RNAPII C-terminal repeat domain (CTD) phosphorylated on both Ser2 and Ser5 and are detected at early, alternative polyA sites. Concomitant knockout of human SCAF4 and SCAF8 results in altered polyA selection and subsequent early termination, leading to expression of truncated mRNAs and proteins lacking functional domains and is cell lethal. While SCAF4 and SCAF8 work redundantly to suppress early mRNA termination, they also have independent, non-essential functions. SCAF8 is an RNAPII elongation factor, whereas SCAF4 is required for correct termination at canonical, distal transcription termination sites in the presence of SCAF8. Together, SCAF4 and SCAF8 coordinate the transition between elongation and termination, ensuring correct polyA site selection and RNAPII transcriptional termination in human cells.
AB - Accurate regulation of mRNA termination is required for correct gene expression. Here, we describe a role for SCAF4 and SCAF8 as anti-terminators, suppressing the use of early, alternative polyadenylation (polyA) sites. The SCAF4/8 proteins bind the hyper-phosphorylated RNAPII C-terminal repeat domain (CTD) phosphorylated on both Ser2 and Ser5 and are detected at early, alternative polyA sites. Concomitant knockout of human SCAF4 and SCAF8 results in altered polyA selection and subsequent early termination, leading to expression of truncated mRNAs and proteins lacking functional domains and is cell lethal. While SCAF4 and SCAF8 work redundantly to suppress early mRNA termination, they also have independent, non-essential functions. SCAF8 is an RNAPII elongation factor, whereas SCAF4 is required for correct termination at canonical, distal transcription termination sites in the presence of SCAF8. Together, SCAF4 and SCAF8 coordinate the transition between elongation and termination, ensuring correct polyA site selection and RNAPII transcriptional termination in human cells.
KW - HEK293 Cells
KW - Humans
KW - Poly A/genetics
KW - Protein Domains
KW - RNA Polymerase II/genetics
KW - RNA, Messenger/biosynthesis
KW - RNA-Binding Proteins/genetics
KW - Serine-Arginine Splicing Factors/genetics
KW - Transcription Elongation, Genetic
KW - Transcription Termination, Genetic
U2 - 10.1016/j.cell.2019.04.038
DO - 10.1016/j.cell.2019.04.038
M3 - Journal article
C2 - 31104839
VL - 177
SP - 1797-1813.e18
JO - Cell
JF - Cell
SN - 0092-8674
IS - 7
ER -
ID: 328236328