Affordable Access

deepdyve-link
Publisher Website

Mechanism of Nonsense-Mediated mRNA Decay Stimulation by Splicing Factor SRSF1.

Authors
  • Aznarez, Isabel1
  • Nomakuchi, Tomoki T1
  • Tetenbaum-Novatt, Jaclyn1
  • Rahman, Mohammad Alinoor1
  • Fregoso, Oliver1
  • Rees, Holly1
  • Krainer, Adrian R2
  • 1 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
  • 2 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
May 15, 2018
Volume
23
Issue
7
Pages
2186–2198
Identifiers
DOI: 10.1016/j.celrep.2018.04.039
PMID: 29768215
Source
Medline
Keywords
License
Unknown

Abstract

The splicing factor SRSF1 promotes nonsense-mediated mRNA decay (NMD), a quality control mechanism that degrades mRNAs with premature termination codons (PTCs). Here we show that transcript-bound SRSF1 increases the binding of NMD factor UPF1 to mRNAs while in, or associated with, the nucleus, bypassing UPF2 recruitment and promoting NMD. SRSF1 promotes NMD when positioned downstream of a PTC, which resembles the mode of action of exon junction complex (EJC) and NMD factors. Moreover, splicing and/or EJC deposition increase the effect of SRSF1 on NMD. Lastly, SRSF1 enhances NMD of PTC-containing endogenous transcripts that result from various events. Our findings reveal an alternative mechanism for UPF1 recruitment, uncovering an additional connection between splicing and NMD. SRSF1's role in the mRNA's journey from splicing to decay has broad implications for gene expression regulation and genetic diseases.

Report this publication

Statistics

Seen <100 times