SCAF4 and SCAF8, mRNA Anti-Terminator Proteins
Open accessAbstract
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.
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In mammalian cells most studies only consider very long genes to accurately decipher an elongation speed.
“Indeed, in mammalian cells most studies only consider very long genes to accurately decipher an elongation speed (Saponaro et al, 2014; Cortazar et al, 2019; Gregersen et al, 2019; Hou et al, 2019; Sheridan et al, 2019; Fan et al, 2020).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Gregersen et al, 2019
The STAR★Methods section (page not provided) says the study selected genes 60–300 kb long for its DRB/TT-seq elongation analysis, and the Results report elongation rates calculated from long genes. This supports Gregersen et al. as an example, but the paper does not establish that most mammalian-cell studies use very long genes or explicitly say that doing so is necessary for accuracy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSCAF8 is a positive RNA Pol II elongation factor that increases RNA Pol II speed.
“SCAF8, an RNA Pol II CTD‐interacting protein, which plays a role in suppressing the use of proximal poly(A) sites, is a positive RNA Pol II elongation factor that increases RNA Pol II speed (Gregersen et al, 2019).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Gregersen et al, 2019
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- Authors
- Gregersen, L. H., Mitter, R., Ugalde, A. P., Nojima, T., Proudfoot, N. J., Agami, R., Stewart, A., & Svejstrup, J. Q.
- Affiliations
- The Francis Crick Institute (GB)
- The Netherlands Cancer Institute (NL)
- University of Oxford (GB)
- Corresponding author
- Svejstrup, Jesper Q.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 177
- Issue
- 7
- Pages
- 1797-1813.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6579486
- OpenAlex
- W2944834243
- Cited by
- 140
- References
- 73
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 29 · 2023: 22 · 2022: 16 · 2021: 19 · 2020: 13 · 2019: 5
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- The Francis Crick Institute (cc-by)
- Funders
- Francis Crick Institute
- Cancer Research UK (FC001166)
- Medical Research Council (FC001166)
- Wellcome Trust (FC001166)
- European Research Council (Agreement 693327)
- EMBO-LTF program (EMBO ALTF 1026-2014)
- The Human Frontier Science Program (LT000640/2013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- polyadenylation site selection, RNA polymerase II C-terminal domain phosphorylation, transcription termination, transcription elongation, truncated mRNA, gene expression regulation
- MeSH terms
- Serine-Arginine Splicing Factors, Protein Domains, Humans, Poly A, RNA Polymerase II, RNA, Messenger, RNA-Binding Proteins, HEK293 Cells, Transcription Elongation, Genetic, Transcription Termination, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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