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RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits

查看全文 作　　者：Yue [1,2,3,4]Lv;Gang [3]Lu;Yuling [2,4]Cai;Ruibao [5,6]Su;Liang [5]Liang;Xin [7]Wang;Wenyu [2,4]Mu;Xiuqing [2,4]He;Tao [2,4]Huang;Jinlong [2,3,4]Ma;Yueran [1,2,4]Zhao;Zi-Jiang [1,2,4,8,9]Chen;Yuanchao [5]Xue;Hongbin [2,3,4]Liu;Wai-Yee [3]Chan 高影响力作者 机构地区：[1]Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250012,China;[2]Center for Reproductive Medicine,Shandong University,Jinan 250012,China;[3]CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong,China;[4]Key Laboratory of Reproductive Endocrinology of Ministry of Education,Shandong University,Jinan 250012,China;[5]Key Laboratory of RNA Biology,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;[6]Fertility Preservation Lab,Reproductive Medicine Center,Guangdong Second Provincial General Hospital,Guangzhou 510062,China;[7]Key Laboratory of Systems Health Science of Zhejiang Province,School of Life Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China;[8]Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics,Shanghai 200135,China;[9]Center for Reproductive Medicine,Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200135,China高影响力机构 出　　处：《Protein & Cell》索引2023年第14卷第1期,共13页高影响力期刊 基　　金：supported by grants from the National Key R&D Program of China(2021YFC2700200);Academic Promotion Programme of Shandong First Medical University(2019U001);General Research Fund from Research Grants Council of Hong Kong(14103418);Basic Science Center Program of NFSC(31988101);the Shandong Provincial Key Research and Development Program(2020ZLYS02);a fund from A-Smart Group to support CUHKSDU Joint Laboratory on Reproductive Genetics of CUHK,Major Innovation Projects in Shandong Province(2021ZDSYS16);the Science Foundation for Distinguished Yong Scholars of Shandong(ZR2021JQ27);Taishan Scholars Program for Young Experts of Shandong Province(tsqn202103192). 摘　　要：RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis,but the targets and molecular functions of RBM46 remain unknown.Here,we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation.Using a recently reported,high-resolution technique known as LACE-seq and working with low-input cells,we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes.We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions.In Rbm46 knockout mice,the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation,resulting in the failed assembly of axial elements,synapsis disruption,and meiotic arrest.Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials. 关 键 词：RBM46 LACE-seq RNA-binding protein MEIOSIS COHESIN
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