Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function
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 sign...
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doaj-845f0738991141b2b17f24634db904622021-08-09T16:32:19ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.65104Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia functionFiona Haward0https://orcid.org/0000-0001-9048-5600Magdalena M Maslon1https://orcid.org/0000-0002-1050-1306Patricia L Yeyati2Nicolas Bellora3https://orcid.org/0000-0001-6637-3465Jan N Hansen4https://orcid.org/0000-0002-0489-7535Stuart Aitken5Jennifer Lawson6Alex von Kriegsheim7Dagmar Wachten8https://orcid.org/0000-0003-4800-6332Pleasantine Mill9Ian R Adams10https://orcid.org/0000-0001-8838-1271Javier F Caceres11https://orcid.org/0000-0001-8025-6169MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomInstitute of Nuclear Technologies for Health (Intecnus), National Scientific and Technical Research Council (CONICET), Bariloche, ArgentinaInstitute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, GermanyMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomEdinburgh Cancer Research United Kingdom Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomInstitute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, GermanyMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomShuttling 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 and tissues 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.https://elifesciences.org/articles/65104SR proteinsSRSF1RNA-binding proteinsalternative splicingmRNA translationmotile cilia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fiona Haward Magdalena M Maslon Patricia L Yeyati Nicolas Bellora Jan N Hansen Stuart Aitken Jennifer Lawson Alex von Kriegsheim Dagmar Wachten Pleasantine Mill Ian R Adams Javier F Caceres |
spellingShingle |
Fiona Haward Magdalena M Maslon Patricia L Yeyati Nicolas Bellora Jan N Hansen Stuart Aitken Jennifer Lawson Alex von Kriegsheim Dagmar Wachten Pleasantine Mill Ian R Adams Javier F Caceres Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function eLife SR proteins SRSF1 RNA-binding proteins alternative splicing mRNA translation motile cilia |
author_facet |
Fiona Haward Magdalena M Maslon Patricia L Yeyati Nicolas Bellora Jan N Hansen Stuart Aitken Jennifer Lawson Alex von Kriegsheim Dagmar Wachten Pleasantine Mill Ian R Adams Javier F Caceres |
author_sort |
Fiona Haward |
title |
Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function |
title_short |
Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function |
title_full |
Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function |
title_fullStr |
Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function |
title_full_unstemmed |
Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function |
title_sort |
nucleo-cytoplasmic shuttling of splicing factor srsf1 is required for development and cilia function |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-08-01 |
description |
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 and tissues 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. |
topic |
SR proteins SRSF1 RNA-binding proteins alternative splicing mRNA translation motile cilia |
url |
https://elifesciences.org/articles/65104 |
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