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

Aznarez, Isabel, Nomakuchi, Tomoki T., Tetenbaum-Novatt, Jaclyn, Rahman, Mohammad Alinoor, Fregoso, Oliver, Rees, Holly, Krainer, Adrian R. (May 2018) Mechanism of Nonsense-Mediated mRNA Decay Stimulation by Splicing Factor SRSF1. Cell Reports, 23 (7). pp. 2186-2198. ISSN 2211-1247

DOI: 10.1016/j.celrep.2018.04.039


Summary 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.

Item Type: Paper
Uncontrolled Keywords: NMD RNA splicing SRSF1 UPF1 EJC
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Inheritance Program
CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
CSHL labs > Krainer lab
School of Biological Sciences > Publications
CSHL Cancer Center Shared Resources > Animal Shared Resource
Depositing User: Matt Covey
Date: 15 May 2018
Date Deposited: 21 May 2018 20:33
Last Modified: 09 Nov 2020 21:43
PMCID: PMC5999336
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