title: RAN-binding protein 9 is involved in alternative splicing and is critical for male germ cell development and male fertility.
abstract: As a member of the large Ran-binding protein family, Ran-binding protein 9 (RANBP9) has been suggested to play a critical role in diverse cellular functions in somatic cell lineages in vitro, and this is further supported by the neonatal lethality phenotype in Ranbp9 global knockout mice. However, the exact molecular actions of RANBP9 remain largely unknown. By inactivation of Ranbp9 specifically in testicular somatic and spermatogenic cells, we discovered that Ranbp9 was dispensable for Sertoli cell development and functions, but critical for male germ cell development and male fertility. RIP-Seq and proteomic analyses revealed that RANBP9 was associated with multiple key splicing factors and directly targeted >2,300 mRNAs in spermatocytes and round spermatids. Many of the RANBP9 target and non-target mRNAs either displayed aberrant splicing patterns or were dysregulated in the absence of Ranbp9. Our data uncovered a novel role of Ranbp9 in regulating alternative splicing in spermatogenic cells, which is critical for normal spermatogenesis and male fertility.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Chong
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Bhupal P
authors.initials: BP
authors.lastname: Bhetwal
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Huili
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, Nevada, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D005298:Fertility / Q000235:genetics*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D013087:Spermatids / Q000378:metabolism; D013090:Spermatocytes / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9