The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly in myogenesis
Autor: | Patrick Brien, Hema Bye-A-Jee, Dhamayanthi Pugazhendhi, Jennifer Pell, Samuel Woodhouse, Rachel A. Watson, Martin R Turner |
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Přispěvatelé: | Apollo - University of Cambridge Repository, Turner, Martin [0000-0002-3801-9896] |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine lcsh:Diseases of the musculoskeletal system Satellite Cells Skeletal Muscle Injury RNA-binding protein Biology Cell fate determination Muscle Development Zfp36L1 Mice 03 medical and health sciences 0302 clinical medicine Tristetraprolin Satellite cells Conditional gene knockout Gene expression Zfp36L2 medicine Regeneration Animals Myocyte Orthopedics and Sports Medicine RNA Messenger Muscle Skeletal Molecular Biology Cells Cultured Messenger RNA Myogenesis Research Nuclear Proteins PAX7 Transcription Factor RNA-Binding Proteins Skeletal muscle Cell Differentiation Cell Biology Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure RNA Female lcsh:RC925-935 Skeletal muscle stem cells Butyrate Response Factor 1 030217 neurology & neurosurgery |
Zdroj: | Skeletal Muscle, Vol 8, Iss 1, Pp 1-12 (2018) Skeletal Muscle |
DOI: | 10.17863/cam.33891 |
Popis: | Background Members of the ZFP36 family of RNA-binding proteins regulate gene expression post-transcriptionally by binding to AU-rich elements in the 3’UTR of mRNA and stimulating mRNA degradation. The proteins within this family target different transcripts in different tissues. In particular, ZFP36 targets myogenic transcripts and may have a role in adult muscle stem cell quiescence. Our study examined the requirement of ZFP36L1 and ZFP36L2 in adult muscle cell fate regulation. Methods We generated single and double conditional knockout mice in which Zfp36l1 and/or Zfp36l2 were deleted in Pax7-expressing cells. Immunostained muscle sections were used to analyse resting skeletal muscle, and a cardiotoxin-induced injury model was used to determine the regenerative capacity of muscle. Results We show that ZFP36L1 and ZFP36L2 proteins are expressed in satellite cells. Mice lacking the two proteins in Pax7-expressing cells have reduced body weight and have reduced skeletal muscle mass. Furthermore, the number of satellite cells is reduced in adult skeletal muscle and the capacity of this muscle to regenerate following muscle injury is diminished. Conclusion ZFP36L1 and ZFP36L2 act redundantly in myogenesis. These findings add further intricacy to the regulation of the cell fate of Pax7-expressing cells in skeletal muscle by RNA-binding proteins. Electronic supplementary material The online version of this article (10.1186/s13395-018-0183-9) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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