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A micro RNA cluster in the Fragile‐X region expressed during spermatogenesis targets FMR 1
Author(s) -
Ramaiah Madhuvanthi,
Tan Kun,
Plank TerraDawn M,
Song HyeWon,
Chousal Jennifer N,
Jones Samantha,
Shum Eleen Y,
Sheridan Steven D,
Peterson Kevin J,
Gromoll Jörg,
Haggarty Stephen J,
CookAndersen Heidi,
Wilkinson Miles F
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846566
Subject(s) - cluster (spacecraft) , rna , spermatogenesis , microbiology and biotechnology , biology , chemistry , genetics , gene , computer science , computer network , endocrinology
Testis‐expressed X‐linked genes typically evolve rapidly. Here, we report on a testis‐expressed X‐linked micro RNA (mi RNA ) cluster that despite rapid alterations in sequence has retained its position in the Fragile‐X region of the X chromosome in placental mammals. Surprisingly, the mi RNA s encoded by this cluster ( Fx‐mir ) have a predilection for targeting the immediately adjacent gene, Fmr1 , an unexpected finding given that mi RNA s usually act in trans , not in cis . Robust repression of Fmr1 is conferred by combinations of Fx‐mir mi RNA s induced in Sertoli cells ( SC s) during postnatal development when they terminate proliferation. Physiological significance is suggested by the finding that FMRP , the protein product of Fmr1 , is downregulated when Fx‐mir mi RNA s are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx‐mir mi RNA s not only regulate the expression of FMRP , but also regulate the expression of eIF 4E and CYFIP 1, which together with FMRP form a translational regulatory complex. Our results support a model in which Fx‐mir family members act cooperatively to regulate the translation of batteries of mRNA s in a developmentally regulated manner in SC s.