Translational activity of the splicing factor SRSF1 is required for development and cilia function
Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. SR proteins regulate pre-mRNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significan...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/183650 |
| Acceso en línea: | http://hdl.handle.net/11336/183650 |
| Access Level: | acceso abierto |
| Palabra clave: | COMPUTATIONAL GENOMICS SR PROTEINS SRSF1 ALTERNATIVE SPLICING MRNA TRANSLATION CILIA https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Sumario: | Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. SR proteins regulate pre-mRNA 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 Srsf1 to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus. Srsf1NRS/NRS mutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility. These results highlight the physiological requirement of splicing factor shuttling to reprogram gene expression networks at the level of mRNA translation in the context of high cellular demand for cilia function. |
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