Mex3c regulates insulin-like growth factor 1 (IGF1) expression and promotes postnatal growth.
Mex3c regulates insulin-like growth factor 1 (IGF1) expression and promotes postnatal growth.
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DOI：
10.1091/mbc.e11-11-0960
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发表时间：
2012-04
影响因子：
3.3
通讯作者：
Lu B
中科院分区：
文献类型：
--
作者：
Jiao Y;Bishop CE;Lu B
Mex3c在睾丸、大脑和发育中的骨骼中高度表达。Mex3c突变导致出生后生长迟缓和背景依赖性围产期死亡，可能是通过破坏骨形成细胞中胰岛素样生长因子1 mRNA的翻译。胰岛素样生长因子1 （IGF1）介导生长激素的促生长活性。Igf1的表达如何在转录后调控尚不清楚。秀丽隐杆线虫肌肉过剩3 （MEX-3）通过调控参与细胞命运的mrna参与胚胎早期发育过程中细胞命运的指定。其哺乳动物同源物MEX3C的功能尚不清楚。本研究表明，MEX3C纯合突变小鼠的MEX3C缺陷会导致出生后生长迟缓和背景依赖性围产期死亡。生长板中软骨细胞的肥厚明显受损。在突变小鼠中，IGF1的循环和骨局部生成均减少。Mex3c mRNA在睾丸和大脑中强烈表达，在生长板的静息和增殖软骨细胞中高度表达。MEX3C能够从组织裂解物中富集多种mRNA物种，包括Igf1。Igf1在骨中的表达在蛋白水平下降，但在mRNA水平上没有下降，表明翻译/翻译后调控。我们认为，MEX3C蛋白在增强Igf1 mRNA的翻译中发挥重要作用，这解释了MEX3C缺陷小鼠的围产期死亡和生长迟缓。
Mex3c is highly expressed in the testis, brain, and developing bone. Mex3c mutation causes postnatal growth retardation and background-dependent perinatal lethality, possibly through impairing the translation of insulin-like growth factor 1 mRNA in bone-forming cells. Insulin-like growth factor 1 (IGF1) mediates the growth-promoting activities of growth hormone. How Igf1 expression is regulated posttranscriptionally is unclear. Caenorhabditis elegans muscle excess 3 (MEX-3) is involved in cell fate specification during early embryonic development through regulating mRNAs involved in specifying cell fate. The function of its mammalian homologue, MEX3C, is unknown. Here we show that MEX3C deficiency in Mex3c homozygous mutant mice causes postnatal growth retardation and background-dependent perinatal lethality. Hypertrophy of chondrocytes in growth plates is significantly impaired. Circulating and bone local production of IGF1 are both decreased in mutant mice. Mex3c mRNA is strongly expressed in the testis and the brain, and highly expressed in resting and proliferating chondrocytes of the growth plates. MEX3C is able to enrich multiple mRNA species from tissue lysates, including Igf1. Igf1 expression in bone is decreased at the protein level but not at the mRNA level, indicating translational/posttranslational regulation. We propose that MEX3C protein plays an important role in enhancing the translation of Igf1 mRNA, which explains the perinatal lethality and growth retardation observed in MEX3C-deficient mice.