SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal

Tingsheng Yu, Oscar Cazares, Alison D. Tang, Hyun Yi Kim, Tomas Wald, Adya Verma, Qi Liu, Mary Helen Barcellos-Hoff, Stephen N. Floor, Han Sung Jung, Angela N. Brooks, Ophir D. Klein

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)624-637.e4
JournalDevelopmental Cell
Volume57
Issue number5
DOIs
Publication statusPublished - 2022 Mar 14

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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