Mechanism of Nonsense-Mediated mRNA Decay Stimulation by Splicing Factor SRSF1
| Autor: | Oliver I. Fregoso, Mohammad Alinoor Rahman, Jaclyn Tetenbaum-Novatt, Adrian R. Krainer, Tomoki T. Nomakuchi, Holly A. Rees, Isabel Aznarez |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Nonsense-mediated decay Amino Acid Motifs Endogeny General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Splicing factor 0302 clinical medicine medicine Humans RNA Messenger Phosphorylation Regulation of gene expression Cell Nucleus Messenger RNA Models Genetic Serine-Arginine Splicing Factors Chemistry RNA-Binding Proteins Exons Cell biology Nonsense Mediated mRNA Decay Alternative Splicing 030104 developmental biology medicine.anatomical_structure Codon Nonsense RNA splicing Exon junction complex Nucleus 030217 neurology & neurosurgery HeLa Cells Protein Binding Transcription Factors |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| Popis: | 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. Graphical abstract In Brief: Aznarez et al. describe the mechanism behind the enhancement of nonsense-mediated mRNA decay (NMD) by the splicing factor SRSF1. Through its early association with the mRNA in the nucleus and its direct recruitment of UPF1, SRSF1 bypasses some of the steps necessary for the canonical NMD pathway. |
| Databáze: | OpenAIRE |
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