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RNA processing

Captured: the elusive eukaryotic tRNA splicing enzyme

Nature Structural & Molecular Biology (2023)Cite this article

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The maturation of transfer RNAs requires the splicing of precursor tRNAs by specific endonucleases. New cryo-electron microscopy studies of the human splicing endonuclease bound to tRNAs shed light on how it cleaves and splices its substrates, explaining the function of eukaryote-specific enzyme subunits and rationalizing disease-associated mutations.

The protein-catalysed splicing of eukaryotic precursor transfer RNAs (tRNAs) was discovered in 1978 (ref. 1); decades later, the yeast tRNA splicing endonuclease (SEN)2 and its human counterpart (TSEN)3 were found to be heterotetrameric complexes. Crystal structures have since been obtained of archaeal tRNA splicing endonucleases, which consist of dimers or tetramers formed from one or two different subunits4,5,6,7. But structures of the eukaryotic heterotetrameric complexes have been more elusive.

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Fig. 1: Overall structures of the human TSEN–pre-tRNA complex and comparison with its archaeal counterpart.
Fig. 2: Comparison of local structures and interactions at the 3′ splice site.

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Acknowledgements

A.K.H.’s research is supported by a grant from the National Institutes of Health (NIH) National Institute of General Medical Sciences (GM122884). J.Z.’s laboratory is supported by the Intramural Research Program of the NIH and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grant ZIADK075136).

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Authors and Affiliations

  1. Department of Molecular Genetics and Center for RNA Biology, Ohio State University, Columbus, OH, USA

    Anita K. Hopper

  2. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA

    Jinwei Zhang

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  1. Anita K. Hopper
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Correspondence to Anita K. Hopper or Jinwei Zhang.

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Hopper, A.K., Zhang, J. Captured: the elusive eukaryotic tRNA splicing enzyme. Nat Struct Mol Biol (2023). https://doi.org/10.1038/s41594-023-00995-9

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