2. Academic Validation
  3. SCAF4 and SCAF8, mRNA Anti-Terminator Proteins

SCAF4 and SCAF8, mRNA Anti-Terminator Proteins

  • Cell. 2019 Jun 13;177(7):1797-1813.e18. doi: 10.1016/j.cell.2019.04.038.
Lea H Gregersen 1,  Richard Mitter 2,  Alejandro P Ugalde 3,  Takayuki Nojima 4,  Nicholas J Proudfoot 4,  Reuven Agami 3,  Aengus Stewart 2,  Jesper Q Svejstrup 5
Affiliations

Affiliations

  • 1 Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 2 Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 3 The Netherlands Cancer Institute (NKI-AVL), Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
  • 4 Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE Oxford, UK.
  • 5 Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: jesper.svejstrup@crick.ac.uk.
PMID: 31104839 DOI: 10.1016/j.cell.2019.04.038
Abstract

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.

Keywords

C-terminal repeat domain (CTD); CTD phosphorylation; RNA polymerase II; SCAF4; SCAF8; anti-termination; co-transcriptional mRNA processing; polyadenylation; transcript elongation; transcriptional termination.

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