A mark of disease: how mRNA modifications shape genetic and acquired pathologies

Eliana Destefanis; Gülben Avşar; Paula Groza; Antonia Romitelli; Serena Torrini; Pınar Pir; Silvestro G. Conticello; Francesca Aguilo; Erik Dassi

doi:10.1261/rna.077271.120

A mark of disease: how mRNA modifications shape genetic and acquired pathologies

¹Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy
²The EPITRAN COST Action Consortium, COST Action CA16120
³Department of Bioengineering, Gebze Technical University, 41400 Kocaeli, Turkey
⁴Department of Medical Biosciences, Umeå University, 901 87 Umeå, Sweden
⁵Wallenberg Center for Molecular Medicine, Umeå University, 901 87 Umeå, Sweden
⁶Core Research Laboratory, ISPRO—Institute for Cancer Research, Prevention and Clinical Network, 50139 Firenze, Italy
⁷Department of Medical Biotechnologies, Università di Siena, 53100 Siena, Italy
⁸Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy

Corresponding authors: francesca.aguilo{at}umu.se, erik.dassi{at}unitn.it

↵9 These authors contributed equally to this work.

Abstract

RNA modifications have recently emerged as a widespread and complex facet of gene expression regulation. Counting more than 170 distinct chemical modifications with far-reaching implications for RNA fate, they are collectively referred to as the epitranscriptome. These modifications can occur in all RNA species, including messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). In mRNAs the deposition, removal, and recognition of chemical marks by writers, erasers and readers influence their structure, localization, stability, and translation. In turn, this modulates key molecular and cellular processes such as RNA metabolism, cell cycle, apoptosis, and others. Unsurprisingly, given their relevance for cellular and organismal functions, alterations of epitranscriptomic marks have been observed in a broad range of human diseases, including cancer, neurological and metabolic disorders. Here, we will review the major types of mRNA modifications and editing processes in conjunction with the enzymes involved in their metabolism and describe their impact on human diseases. We present the current knowledge in an updated catalog. We will also discuss the emerging evidence on the crosstalk of epitranscriptomic marks and what this interplay could imply for the dynamics of mRNA modifications. Understanding how this complex regulatory layer can affect the course of human pathologies will ultimately lead to its exploitation toward novel epitranscriptomic therapeutic strategies.

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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.077271.120.
Freely available online through the RNA Open Access option.

This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.