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作 者:Siyuan Shen Yanze jian Zhaokui Cai Fudong Li Mengqi Lv Yongrui Liu Jihui Wu Chuanhai Fu Yunyu Shi
机构地区:[1]School of Life Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China [2]MOE key Laboratory for Cellular Dynamics,University of Science&Technology of China,Hefei 230026,China [3]Key Laboratory of RNA Biology,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China
出 处:《Journal of Molecular Cell Biology》2022年第5期27-42,共16页分子细胞生物学报(英文版)
基 金:This work was financially supported by grants from the Ministry of Science and Technology of China(2019YFA0508403);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39010300);the National Natural Science Foundation of China(32090040,31870760,32171222,92149302,U1932122,and 32100958);the China Postdoctoral Science Foundation(2019M662182);the Fundamental Research Funds for the Central Universities(WK2340000097).
摘 要:In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes meiRNA.Previous research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in vivo.However,the underlying mechanisms still remain elusive.We first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 RRM3.We then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro CLIP-seq.These results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)sequence.Furthermore,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.
关 键 词:Mei2 meiRNA MEIOSIS RNA-binding protein CRYSTALLOGRAPHY
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