Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function
Magdalena M Maslon,
Patricia L Yeyati,
Jan N. Hansen,
Alex von Kriegsheim,
Ian R. Adams,
Javier F Caceres
Posted 04 Sep 2020
bioRxiv DOI: 10.1101/2020.09.04.263251
Posted 04 Sep 2020
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 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 in cells derived from this mouse model. These results demonstrate that SRSF1 shuttling is used to reprogram gene expression networks in the context of high cellular demands, as observed here, during motile ciliogenesis.
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