• PMID: 29126923
• Gene Name: CLOCK
• Condition: Involved in spermatogenesis, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Involved in spermatogenesis, Male infertility

CLOCK interacts with RANBP9 and is involved in alternative splicing in spermatogenesis

Yang J, Zhang Z, Zhang Y, Zheng X, Lu Y, Tao D, Liu Y, Ma Y.

The core circadian gene CLOCK plays an important role in regulating male reproduction. However, the underlying mechanism still remains unclear. In the present study, we executed yeast two-hybrid screening using cDNA fragment of CLOCK PAS A domain as bait, and identified RANBP9 as a novel protein interacting with CLOCK. The interaction between CLOCK and RANBP9 was further validated by in vivo and in vitro assays. Previous studies have confirmed that SF3B3 was a RANBP9 interacting protein. Subsequently, our study also found that CLOCK and SF3B3 can interact with each other by co-immunoprecipitation in mouse testis. In order to dissect the underlying mechanism of CLOCK in spermatogenesis, we also performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) in mouse testis. The result of sequence analyses and Gene Ontology enrichment analyses (biological processes) demonstrated that CLOCK can directly bind 186 key mRNA transcripts in mouse spermatogenesis. Taken together, our results firstly showed that CLOCK can interact with RANBP9 and bind with mRNAs, demonstrating that CLOCK is involved in alternative splicing in spermatogenesis. These results reveal a novel mechanism for CLOCK in spermatogenesis. CI - Copyright © 2017 Elsevier B.V. All rights reserved. FAU - Yang, Junbao AU - Yang J AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China; Department of Medical Biology, North Sichuan Medical College, Nanchong, China. FAU - Zhang, Zhiwei AU - Zhang Z AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China. FAU - Zhang, Yingying AU - Zhang Y AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China. FAU - Zheng, Xulei AU - Zheng X AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China. FAU - Lu, Yilu AU - Lu Y AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China. FAU - Tao, Dachang AU - Tao D AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China. FAU - Liu, Yunqiang AU - Liu Y AD - Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China.