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.

中文翻译：

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RNA结合蛋白Zfp36l1和Zfp36l2在肌发生中起多余作用。

背景技术ZFP36家族的RNA结合蛋白的成员通过与mRNA的3'UTR中富含AU的元件结合并刺激mRNA降解来转录后调节基因表达。该家族中的蛋白质靶向不同组织中的不同转录本。特别地，ZFP36靶向肌原性转录本，并且可能在成年肌肉干细胞静止中起作用。我们的研究检查了ZFP36L1和ZFP36L2在成人肌肉细胞命运调控中的需求。方法我们产生了单条件和双条件基因敲除小鼠，其中在Pax7表达细胞中删除了Zfp36l1和/或Zfp36l2。免疫染色的肌肉切片用于分析静息的骨骼肌，而心毒素诱导的损伤模型用于确定肌肉的再生能力。结果我们显示ZFP36L1和ZFP36L2蛋白在卫星细胞中表达。在Pax7表达细胞中缺乏这两种蛋白质的小鼠体重减轻，骨骼肌质量降低。此外，成年骨骼肌中卫星细胞的数量减少，并且在肌肉损伤后该肌肉再生的能力降低。结论ZFP36L1和ZFP36L2在肌发生中起冗余作用。这些发现为RNA结合蛋白对骨骼肌中Pax7表达细胞的细胞命运的调控增加了更多的复杂性。成年骨骼肌中卫星细胞的数量减少，并且在肌肉损伤后该肌肉再生的能力降低。结论ZFP36L1和ZFP36L2在肌发生中起冗余作用。这些发现为RNA结合蛋白对骨骼肌中Pax7表达细胞的细胞命运的调控增加了更多的复杂性。成年骨骼肌中卫星细胞的数量减少，并且在肌肉损伤后该肌肉再生的能力降低。结论ZFP36L1和ZFP36L2在肌发生中起冗余作用。这些发现为RNA结合蛋白对骨骼肌中Pax7表达细胞的细胞命运的调控增加了更多的复杂性。