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Franz et al. J Transl Genet Genom 2020;4:50-70 Journal of Translational
DOI: 10.20517/jtgg.2020.13 Genetics and Genomics

Review Open Access

Role of transfer RNA modification and

aminoacylation in the etiology of congenital
intellectual disability

Martin Franz , Lisa Hagenau , Lars R. Jensen, Andreas W. Kuss
#
#
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine
Greifswald, Greifswald 17475, Germany.
#Authors cotributed equally.

Correspondence to: Prof. Andreas W. Kuss; Dr. Lars R. Jensen, Department of Functional Genomics, University Medicine
Greifswald, C_FunGene, Felix-Hausdorff-Str. 8, Greifswald 17475, Germany.
E-mail: kussa@uni-greifswald.de; jensenl@uni-greifswald.de

How to cite this article: Franz M, Hagenau L, Jensen LR, Kuss AW. Role of transfer RNA modification and aminoacylation in
the etiology of congenital intellectual disability. J Transl Genet Genom 2020;4:50-70.
http://dx.doi.org/10.20517/jtgg.2020.13

Received: 14 Feb 2020 First Decision: 17 Mar 2020 Revised: 30 Mar 2020 Accepted: 23 Apr 2020 Available online: 16 May 2020
Science Editor: Tjitske Kleefstra Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Transfer RNA (tRNA) modification and aminoacylation are post-transcriptional processes that play a crucial role
in the function of tRNA and thus represent critical steps in gene expression. Knowledge of the exact processes
and effects of the defects in various tRNAs remains incomplete, but a rapidly increasing number of publications
over the last decade has shown a growing amount of evidence as to the importance of tRNAs for normal human
development, including brain formation and the development and maintenance of higher cognitive functions as
well. In this review, we present a synopsis of the literature focusing on tRNA-modifying enzymes and aminoacyl-
tRNA synthetases (ARSs) that have been found to be involved in the etiology of hereditary forms of intellectual
disability. Our overview shows several parallels but also differences in the symptomatic spectrum observed
in individuals affected by intellectual disability caused by mutations in tRNA modifier and/or ARS genes. This
observation suggests that tRNAs seem to assume diverse roles in a variety of cellular processes possibly even
beyond translation and that not only the abundance but also the modification and aminoacylation levels of tRNAs
contribute to cell functions in ways that still remain to be understood.

Keywords: transfer RNA modification, aminoacylation, intellectual disability, aminoacyl-tRNA synthetases, ARS, human
cognition, cognitive impairment, brain development

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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