Matching tRNA modifications in humans to their known and predicted enzymes

de Crécy-Lagard, Valérie; Boccaletto, Pietro; Mangleburg, Carl G; Sharma, Puneet; Lowe, Todd M; Leidel, Sebastian A; Bujnicki, Janusz M (2019). Matching tRNA modifications in humans to their known and predicted enzymes. Nucleic acids research, 47(5), pp. 2143-2159. Oxford University Press 10.1093/nar/gkz011

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tRNA are post-transcriptionally modified by chemical modifications that affect all aspects of tRNA biology. An increasing number of mutations underlying human genetic diseases map to genes encoding for tRNA modification enzymes. However, our knowledge on human tRNA-modification genes remains fragmentary and the most comprehensive RNA modification database currently contains information on approximately 20% of human cytosolic tRNAs, primarily based on biochemical studies. Recent high-throughput methods such as DM-tRNA-seq now allow annotation of a majority of tRNAs for six specific base modifications. Furthermore, we identified large gaps in knowledge when we predicted all cytosolic and mitochondrial human tRNA modification genes. Only 48% of the candidate cytosolic tRNA modification enzymes have been experimentally validated in mammals (either directly or in a heterologous system). Approximately 23% of the modification genes (cytosolic and mitochondrial combined) remain unknown. We discuss these 'unidentified enzymes' cases in detail and propose candidates whenever possible. Finally, tissue-specific expression analysis shows that modification genes are highly expressed in proliferative tissues like testis and transformed cells, but scarcely in differentiated tissues, with the exception of the cerebellum. Our work provides a comprehensive up to date compilation of human tRNA modifications and their enzymes that can be used as a resource for further studies.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Sharma, Puneet and Leidel, Sebastian Andreas

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0305-1048

Publisher:

Oxford University Press

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

13 Jan 2020 08:56

Last Modified:

01 Sep 2020 21:50

Publisher DOI:

10.1093/nar/gkz011

PubMed ID:

30698754

BORIS DOI:

10.7892/boris.137060

URI:

https://boris.unibe.ch/id/eprint/137060

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