The splicing factor SRSF3 is functionally connected to the nuclear RNA exosome for intronless mRNA decay

Scientific Reports
Fabrice MureHenri Gruffat

Abstract

The RNA exosome fulfills important functions in the processing and degradation of numerous RNAs species. However, the mechanisms of recruitment to its various nuclear substrates are poorly understood. Using Epstein-Barr virus mRNAs as a model, we have discovered a novel function for the splicing factor SRSF3 in the quality control of nuclear mRNAs. We have found that viral mRNAs generated from intronless genes are particularly unstable due to their degradation by the nuclear RNA exosome. This effect is counteracted by the viral RNA-binding protein EB2 which stabilizes these mRNAs in the nucleus and stimulates both their export to the cytoplasm and their translation. In the absence of EB2, SRSF3 participates in the destabilization of these viral RNAs by interacting with both the RNA exosome and its adaptor complex NEXT. Taken together, our results provide direct evidence for a connection between the splicing machinery and mRNA decay mediated by the RNA exosome. Our results suggest that SRSF3 aids the nuclear RNA exosome and the NEXT complex in the recognition and degradation of certain mRNAs.

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Citations

Feb 19, 2019·Médecine sciences : M/S·Henri GruffatEvelyne Manet
Jul 17, 2020·Protein & Cell·Ruimin XuShaorong Gao
Aug 7, 2019·Cellular and Molecular Neurobiology·Benedetta PerroneSebastiano Cavallaro
Feb 9, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Rebecca E Wagner, Michaela Frye
Jun 15, 2021·Pathology, Research and Practice·Han Wang, Yanxia Jiang
Dec 24, 2021·Biochemical Society Transactions·Irena SliškovićMichaela Müller-McNicoll
Jan 21, 2022·Nucleic Acids Research·Maria GockertTorben Heick Jensen

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Methods Mentioned

BETA
PCR
transfection
immunoprecipitation
pull down
co-immunoprecipitation
transfections
FACS
PCRs

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