title: Mex3c regulates insulin-like growth factor 1 (IGF1) expression and promotes postnatal growth.
abstract: 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.
authors.affiliation: Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiao
authors.forename: Colin E
authors.initials: CE
authors.lastname: Bishop
authors.forename: Baisong
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006128:Growth / Q000235:genetics; D006132:Growth Plate / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010053:Ovary / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
chemical_list: C575192:MEX3c protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I