• PMID: 28809393
• Gene Name: YTHDC2
• Condition: Regulates mammalian spermatogenesis, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Regulates mammalian spermatogenesis, Male infertility

Ythdc2 is an N(6)-methyladenosine binding protein that regulates mammalian spermatogenesis

Hsu PJ, Zhu Y, Ma H, Guo Y, Shi X, Liu Y, Qi M, Lu Z, Shi H, Wang J, Cheng Y, Luo G, Dai Q, Liu M, Guo X, Sha J, Shen B, He C.

N(6)-methyladenosine (m(6)A) is the most common internal modification in eukaryotic mRNA. It is dynamically installed and removed, and acts as a new layer of mRNA metabolism, regulating biological processes including stem cell pluripotency, cell differentiation, and energy homeostasis. m(6)A is recognized by selective binding proteins; YTHDF1 and YTHDF3 work in concert to affect the translation of m(6)A-containing mRNAs, YTHDF2 expedites mRNA decay, and YTHDC1 affects the nuclear processing of its targets. The biological function of YTHDC2, the final member of the YTH protein family, remains unknown. We report that YTHDC2 selectively binds m(6)A at its consensus motif. YTHDC2 enhances the translation efficiency of its targets and also decreases their mRNA abundance. Ythdc2 knockout mice are infertile; males have significantly smaller testes and females have significantly smaller ovaries compared to those of littermates. The germ cells of Ythdc2 knockout mice do not develop past the zygotene stage and accordingly, Ythdc2 is upregulated in the testes as meiosis begins. Thus, YTHDC2 is an m(6)A-binding protein that plays critical roles during spermatogenesis. FAU - Hsu, Phillip J AU - Hsu PJ AD - Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. AD - Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. AD - Committee on Immunology, The University of Chicago, Chicago, IL 60637, USA. FAU - Zhu, Yunfei AU - Zhu Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Ma, Honghui AU - Ma H AD - Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. AD - Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. FAU - Guo, Yueshuai AU - Guo Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Shi, Xiaodan AU - Shi X AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Liu, Yuanyuan AU - Liu Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Qi, Meijie AU - Qi M AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Lu, Zhike AU - Lu Z AD - Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. AD - Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. FAU - Shi, Hailing AU - Shi H AD - Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. AD - Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. FAU - Wang, Jianying AU - Wang J AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Cheng, Yiwei AU - Cheng Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Luo, Guanzheng AU - Luo G AD - Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. AD - Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. FAU - Dai, Qing AU - Dai Q AD - Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. AD - Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. FAU - Liu, Mingxi AU - Liu M AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Guo, Xuejiang AU - Guo X AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Sha, Jiahao AU - Sha J AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. FAU - Shen, Bin AU - Shen B AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China.