Proteomics

Dataset Information

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Translational activity of the splicing factor SRSF1 is required for development and cilia function


ABSTRACT: The SR protein family of splicing factors regulate constitutive and alternative pre-mRNA splicing. A subset of them, including SRSF1, shuttles continuously between the nucleus and cytoplasm affecting post-splicing processes. We have previously identified a role for SRSF1 in promoting the translation of specific mRNA transcripts, particularly those encoding centrosomal proteins. Here, we used CRISPR/Cas9 editing to knock-in a nuclear retention signal (NRS) in Srsf1 resulting in a non-shuttling SRSF1 mouse model (Srsf1NRS). Srsf1NRS/NRS mice displayed small body size, hydrocephaly and male infertility, all associated with ciliary defects. We observed reduced translation of thousands of mRNAs, in particular of ciliary components, in cells derived from this model. Consistently, we found that the lack of cytoplasmic SRSF1 led to decreased abundance of proteins involved in multiciliogenesis and affected ciliary structure and motility in multiciliated cells. Altogether, these results highlight the physiological relevance of the activity of a splicing factor in the cytoplasm.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Testis, Epithelial Cell

SUBMITTER: Alex von kriegsheim  

LAB HEAD: Alex von Kriegsheim

PROVIDER: PXD019859 | Pride | 2021-08-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
02_SrsfHom-late-1L.raw Raw
02_WT-1-ALI-14L.raw Raw
02_WT-mid-1T.raw Raw
03_Het-2-ALI-14L.raw Raw
03_SrsfHom-late-1T.raw Raw
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Publications


Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. The SR family proteins regulate RNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in <i>Srsf1</i> to create a mouse model harboring an SRSF1 protein that is retained exclusiv  ...[more]

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