Abstract
Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal.
| Original language | English |
|---|---|
| Pages (from-to) | 624-637.e4 |
| Journal | Developmental Cell |
| Volume | 57 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2022 Mar 14 |
Bibliographical note
Funding Information:We thank A. Rathnayake, B. Hoehn, E. Sandoval, and S. Alto for technical assistance, Drs. J. Hu, K. McKinley, P. Marangoni, R. Zwick, T. Huycke, and A. Sharir, members of the Klein, Floor, Brooks, and Goodwin labs for helpful discussions, Dr. K. Seidel for importing and maintaining the Srsf1fl/fl and Srsf3fl/fl mouse lines at the beginning of the project, and the UCSF Functional Genomics Core for help with RNA-seq. This work was funded by NIDCR R01-DE024988 and R35-DE026602 to O.D.K. H.S.J. was supported by National Research Foundation of Korea (NRF) 2016R1A5A2008630. Conceptualization, T.Y. O.C. and O.D.K.; methodology, T.Y. O.C. and O.D.K.; investigation, T.Y. O.C. H.-Y.K. A.D.T. and T.W.; writing–original draft, T.Y. and O.D.K.; writing, review, and editing, T.Y. O.C. H.-Y.K. A.D.T. T.W. Q.L. M.H.B.-H. S.N.F. H.-S.J. A.N.B. and O.D.K.; funding acquisition, O.D.K.; supervision, O.D.K. The authors declare no competing interests. The sex balance of our samples was included as part of our experimental designs. Our laboratories take pride in fostering a diverse and inclusive environment, and we strive to make equitable opportunities for all our trainees. The authors of this paper identify as members of one or more of the following communities: AAPI, Black, Differently Able, Latinx, and LGBTQ+. Also, in this study, one or more of the authors received support from a program designed to increase minority representation.
Funding Information:
We thank A. Rathnayake, B. Hoehn, E. Sandoval, and S. Alto for technical assistance, Drs. J. Hu, K. McKinley, P. Marangoni, R. Zwick, T. Huycke, and A. Sharir, members of the Klein, Floor, Brooks, and Goodwin labs for helpful discussions, Dr. K. Seidel for importing and maintaining the Srsf1 fl/fl and Srsf3 fl/fl mouse lines at the beginning of the project, and the UCSF Functional Genomics Core for help with RNA-seq. This work was funded by NIDCR R01-DE024988 and R35-DE026602 to O.D.K. H.S.J. was supported by National Research Foundation of Korea (NRF) 2016R1A5A2008630 .
Publisher Copyright:
© 2022 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Developmental Biology
- Cell Biology