首页|Molecular mechanism governing RNA-binding property of mammalian TRIM71 protein

Molecular mechanism governing RNA-binding property of mammalian TRIM71 protein

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TRIM71 is an RNA-binding protein with ubiquitin ligase activity.Numerous functions of mammalian TRIM71,including cell cycle regulation,embryonic stem cell(ESC)self-renewal,and reprogramming of pluripotent stem cells,are related to its RNA-binding property.We previously reported that a long non-coding RNA(IncRNA)Trincr1 interacts with mouse TRIM71(mTRIM71)to repress FGF/ERK pathway in mouse ESCs(mESCs).Herein,we identify an RNA motif specifically recognized by mTRIM71 from Trincr1 RNA,and solve the crystal structure of the NHL domain of mTRIM71 complexed with the RNA motif.Similar to the zebrafish TRIM71,mTRIM71 binds to a stem-loop structured RNA fragment of Trincr1,and an adenosine base at the loop region is crucial for the mTRIM71 interaction.We map similar hairpin RNAs preferably bound by TRIM71 in the mRNA UTRs of the cell-cycle related genes regulated by TRIM71.Furthermore,we identify key residues of mTRIM71,conserved among mammalian TRIM71 pro-teins,required for the RNA-binding property.Single-site mutations of these residues significantly impair the binding of TRIM71 to hairpin RNAs in vitro and to mRNAs of Cdkn1a/p21 and Rbl2/p130 in mESCs.Furthermore,congenital hydrocephalus(CH)specific mutation of mTRIM71 impair its binding to the RNA targets as well.These results reveal molecular mechanism behind the recognition of RNA by mam-malian TRIM71 and provide insights into TRIM71 related diseases.

RNA-binding proteinStructureRecognition mechanismDisease-related mutant

Fandi Shi、Kun Zhang、Qixuan Cheng、Shiyou Che、Shuxin Zhi、Zhenyu Yu、Fei Liu、Feifei Duan、Yangming Wang、Na Yang

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State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy,Nankai University,Tianjin 300353,China

Institute of Molecular Medicine,College of Future Technology,Peking University,Beijing 100871,China

College of Chemistry,Tianjin Normal University,Tianjin 300387,China

National Laboratory of Biomacromolecules and Key Laboratory of Epigenetic Regulation and Intervention,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

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Chinese Ministry of Science and Technology,the National Natural Science Foundation of ChinaChinese Ministry of Science and Technology,the National Natural Science Foundation of ChinaChinese Ministry of Science and Technology,the National Natural Science Foundation of ChinaChinese Ministry of Science and Technology,the National Natural Science Foundation of ChinaChinese Ministry of Science and Technology,the National Natural Science Foundation of ChinaHaihe Laboratory of Cell Ecosystem Innovation Fund

2019YFA050890232170549323713152021YFA11002009194030222HHXBSS00021

2024

10.1016/j.scib.2023.11.041

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(1)
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