Publication date: Available online 5 December 2018
Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Jillian Ramos, Dragony Fu
Abstract
A remarkable number of neurodevelopmental disorders have been linked to defects in tRNA modifications. These discoveries place tRNA modifications in the spotlight as critical modulators of gene expression pathways that are required for proper organismal growth and development. Here, we discuss the emerging molecular and cellular functions of the diverse tRNA modifications linked to cognitive and neurological disorders. In particular, we describe how the structure and location of a tRNA modification influences tRNA folding, stability, and function. We then highlight how modifications in tRNA can impact multiple aspects of protein translation that are instrumental for maintaining proper cellular proteostasis. Importantly, we describe how perturbations in tRNA modification lead to a spectrum of deleterious biological outcomes that can disturb neurodevelopment and neurological function. Finally, we summarize the biological themes shared by the different tRNA modifications linked to cognitive disorders and offer insight into the future questions that remain to decipher the role of tRNA modifications. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert.
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