Abstract
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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Impact statement A mouse model where the splicing factor SRSF1 was prevented to accumulate in the cytoplasm revealed reduced translation of thousands of mRNAs and postnatal phenotypes particularly affecting multiciliated cells. This highlights the physiological relevance of nucleo-cytoplasmic shuttling of splicing factors in coordinating nuclear and cytoplasmic events of gene expression.