A microRNA cluster in the Fragile-X region expressed during spermatogenesis targets FMR1.

Autor: Ramaiah M; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Tan K; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Plank TM; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Song HW; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Chousal JN; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Jones S; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Shum EY; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Sheridan SD; Chemical Neurobiology Laboratory, Center for Genomic Medicine, Boston, MA, USA.; Departments of Neurology and Psychiatry, Massachusetts General Hospital, Boston, MA, USA., Peterson KJ; Department of Biological Sciences, Dartmouth College, Hanover, NH, USA., Gromoll J; Center for Reproductive Medicine and Andrology, University of Münster, Münster, Germany., Haggarty SJ; Chemical Neurobiology Laboratory, Center for Genomic Medicine, Boston, MA, USA.; Departments of Neurology and Psychiatry, Massachusetts General Hospital, Boston, MA, USA., Cook-Andersen H; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Wilkinson MF; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA mfwilkinson@ucsd.edu.; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2019 Feb; Vol. 20 (2). Date of Electronic Publication: 2018 Dec 20.
DOI: 10.15252/embr.201846566
Abstrakt: Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed X-linked microRNA (miRNA) 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 miRNAs encoded by this cluster ( Fx-mir ) have a predilection for targeting the immediately adjacent gene, Fmr1 , an unexpected finding given that miRNAs usually act in trans , not in cis Robust repression of Fmr1 is conferred by combinations of Fx-mir miRNAs induced in Sertoli cells (SCs) 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 miRNAs are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx-mir miRNAs not only regulate the expression of FMRP, but also regulate the expression of eIF4E and CYFIP1, 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 mRNAs in a developmentally regulated manner in SCs.
(© 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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