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Modifications of the human tRNA anticodon loop and their associations with genetic diseases

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Abstract

Transfer RNAs (tRNAs) harbor the most diverse posttranscriptional modifications. Among such modifications, those in the anticodon loop, either on nucleosides or base groups, compose over half of the identified posttranscriptional modifications. The derivatives of modified nucleotides and the crosstalk of different chemical modifications further add to the structural and functional complexity of tRNAs. These modifications play critical roles in maintaining anticodon loop conformation, wobble base pairing, efficient aminoacylation, and translation speed and fidelity as well as mediating various responses to different stress conditions. Posttranscriptional modifications of tRNA are catalyzed mainly by enzymes and/or cofactors encoded by nuclear genes, whose mutations are firmly connected with diverse human diseases involving genetic nervous system disorders and/or the onset of multisystem failure. In this review, we summarize recent studies about the mechanisms of tRNA modifications occurring at tRNA anticodon loops. In addition, the pathogenesis of related disease-causing mutations at these genes is briefly described.

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Acknowledgements

The authors would like to acknowledge the published work of many researchers whose work has relevance for this review, but were not cited because of space and our own limitations.

Funding

National Key Research and Development Program of China [2017YFA0504000], Natural Science Foundation of China [91440204, 31500644, 31570792, 31670801, 31822015, 81870896, 31870811], Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19010203], Shanghai Key Laboratory of Embryo Original Diseases [Shelab201904], Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University [ZDFY2020-RG-0003].

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Authors and Affiliations

  1. State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China

    Jing-Bo Zhou, En-Duo Wang & Xiao-Long Zhou

  2. School of Life Science and Technology, ShanghaiTech University, 93 Middle Huaxia Road, Shanghai, 201210, China

    En-Duo Wang

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  1. Jing-Bo Zhou
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  2. En-Duo Wang
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  3. Xiao-Long Zhou
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ZJB and ZXL wrote the manuscript. All authors approved the manuscript.

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Correspondence to En-Duo Wang or Xiao-Long Zhou.

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Zhou, JB., Wang, ED. & Zhou, XL. Modifications of the human tRNA anticodon loop and their associations with genetic diseases. Cell. Mol. Life Sci. 78, 7087–7105 (2021). https://doi.org/10.1007/s00018-021-03948-x

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