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Cited by 16RNA Research and SplicingRNA regulation and diseaseCancer-related molecular mechanisms research

The discovery, function, and regulation of epithelial splicing regulatory proteins (ESRP) 1 and 2

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Derham, Jessica M., Kalsotra, Auinash·2023·Biochemical Society Transactions
DOI 10.1042/bst20221124PMC PMC11298080
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Abstract

Alternative splicing is a broad and evolutionarily conserved mechanism to diversify gene expression and functionality. The process relies on RNA binding proteins (RBPs) to recognize and bind target sequences in pre-mRNAs, which allows for the inclusion or skipping of various alternative exons. One recently discovered family of RBPs is the epithelial splicing regulatory proteins (ESRP) 1 and 2. Here, we discuss the structure and physiological function of the ESRPs in a variety of contexts. We emphasize the current understanding of their splicing activities, using the classic example of fibroblast growth factor receptor 2 mutually exclusive splicing. We also describe the mechanistic roles of ESRPs in coordinating the splicing and functional output of key signaling pathways that support the maintenance of, or shift between, epithelial and mesenchymal cell states. In particular, we highlight their functions in the development of mammalian limbs, the inner ear, and craniofacial structure while discussing the genetic and biochemical evidence that showcases their conserved roles in tissue regeneration, disease, and cancer pathogenesis.

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  • Most epithelial tissues express both ESRP1 and ESRP2, but the liver is unique, as ESRP2 is the sole paralog present in human and mouse hepatocytes.

    “Most epithelial tissues express both ESRP1 and ESRP2, but the liver is unique, as ESRP2 is the sole paralog present in human and mouse hepatocytes (Derham and Kalsotra 2023).”

    From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Derham and Kalsotra 2023

    In “Physiological Functions of ESRPs” (page unavailable), the review says the two paralogs are typically co-expressed and that ESRP2 is the sole paralog expressed in the liver. It discusses hepatocytes and mouse experiments, but does not explicitly establish that ESRP2 is the sole paralog in both human and mouse hepatocytes. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Derham, J. M., & Kalsotra, A.
Affiliations
University of Illinois Urbana-Champaign (US)
Corresponding author
Kalsotra, Auinash
ORCID
Venue
Biochemical Society Transactions
Publisher
Portland Press Ltd.
Published
2023-06-14
Volume
51
Issue
3
Pages
1097-1109
ISSN
  • 0300-5127 (ISSN-L)
  • 1470-8752
DOI
10.1042/bst20221124
PMC
PMC11298080
OpenAlex
W4380576653
Cited by
16
References
7
Citations by year
2026: 4 · 2025: 9 · 2024: 3
FWCI
1.43
Type
journal article
Language
en
Open access
Locations
  • Biochemical Society Transactions (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Illinois at Urbana-Champaign
  • National Institute on Alcohol Abuse and Alcoholism (R01AA010154)
  • National Heart, Lung, and Blood Institute (R01HL126845)
  • Center for Advanced Study, University of Illinois at Urbana-Champaign
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD104039)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
ESRP1, ESRP2, alternative splicing, RNA-binding proteins, FGFR2, epithelial-mesenchymal transition, limb development, inner ear development, craniofacial development, tissue regeneration, cancer, gene expression regulation
MeSH terms
Animals, Humans, Mammals, Neoplasms, RNA Splicing, Transcription Factors, RNA-Binding Proteins, Alternative Splicing

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