PUBLICATION

Molecular mechanism governing RNA-binding property of mammalian TRIM71 protein

Authors
Shi, F., Zhang, K., Cheng, Q., Che, S., Zhi, S., Yu, Z., Liu, F., Duan, F., Wang, Y., Yang, N.
ID
ZDB-PUB-231201-11
Date
2023
Source
Science Bulletin   69(1): 72-81 (Journal)
Registered Authors
Keywords
Disease-related mutant, RNA-binding protein, Recognition mechanism, Structure
MeSH Terms
  • RNA-Binding Proteins/genetics
  • Tripartite Motif Proteins/genetics
  • Animals
  • RNA
  • Zebrafish*/genetics
  • Ubiquitin-Protein Ligases*/genetics
  • Mice
  • Mammals/genetics
(all 8)
PubMed
38036331 Full text @ Science Bull.
Abstract
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 noncoding RNA (lncRNA) 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 proteins, 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 mammalian TRIM71 and provide insights into TRIM71 related diseases.
Genes / Markers
Figures
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Fish
Antibodies
Orthology
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Mapping
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Citation
Shi, F., Zhang, K., Cheng, Q., Che, S., Zhi, S., Yu, Z., Liu, F., Duan, F., Wang, Y., Yang, N. (2023) Molecular mechanism governing RNA-binding property of mammalian TRIM71 protein. Science Bulletin. 69(1):72-81.