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

Protein & Cell 2023年第1期14卷 51-63页

作者： Yue Lv Gang Lu Yuling Cai Ruibao Su Liang Liang Xin Wang Wenyu Mu Xiuqing He Tao Huang Jinlong Ma Yueran Zhao Zi-Jiang Chen Yuanchao Xue Hongbin Liu Wai-Yee Chan Shandong Key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250012China Center for Reproductive Medicine Shandong UniversityJinan 250012China CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong KongChina Key Laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Fertility Preservation Lab Reproductive Medicine CenterGuangdong Second Provincial General HospitalGuangzhou 510062China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Shanghai 200135China Center for Reproductive Medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200135China

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis,but the targets and molecular functions of RBM46 remain ***,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 *** 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 *** found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs *** 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 *** 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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