2024-03-28T13:29:42Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:02002176
2023-01-16T04:44:05Z
499:500:501
Regulated splicing of large exons is linked to phase‐separation of vertebrate transcription factors
Kawachi, Toshihiko
Masuda, Akio
Yamashita, Yoshihiro
Takeda, Jun‐ichi
Ohkawara, Bisei
Ito, Mikako
Ohno, Kinji
open access
Although large exons cannot be readily recognized by the spliceosome, many are evolutionarily conserved and constitutively spliced for inclusion in the processed transcript. Furthermore, whether large exons may be enriched in a certain subset of proteins, or mediate specific functions, has remained unclear. Here, we identify a set of nearly 3,000 SRSF3-dependent large constitutive exons (S3-LCEs) in human and mouse cells. These exons are enriched for cytidine-rich sequence motifs, which bind and recruit the splicing factors hnRNP K and SRSF3. We find that hnRNP K suppresses S3-LCE splicing, an effect that is mitigated by SRSF3 to thus achieve constitutive splicing of S3-LCEs. S3-LCEs are enriched in genes for components of transcription machineries, including mediator and BAF complexes, and frequently contain intrinsically disordered regions (IDRs). In a subset of analyzed S3-LCE-containing transcription factors, SRSF3 depletion leads to deletion of the IDRs due to S3-LCE exon skipping, thereby disrupting phase-separated assemblies of these factors. Cytidine enrichment in large exons introduces proline/serine codon bias in intrinsically disordered regions and appears to have been evolutionarily acquired in vertebrates. We propose that layered splicing regulation by hnRNP K and SRSF3 ensures proper phase-separation of these S3-LCE-containing transcription factors in vertebrates.
Published online; 4 October 2021
Wiley
2022-04-04
2021-11-15
eng
journal article
AM
http://hdl.handle.net/2237/0002002176
https://nagoya.repo.nii.ac.jp/records/2002176
https://doi.org/10.15252/embj.2020107485
0261-4189
The EMBO Journal
40
22
e107485
https://nagoya.repo.nii.ac.jp/record/2002176/files/EMBOJ-2020-107485R-MS_file.pdf
application/pdf
6.1 MB
2022-04-04