Contribution of A-to-I RNA editing, M6A RNA Methylation, and Alternative Splicing to physiological brain aging and neurodegenerative diseases

Valentina Tassinari; Piergiorgio La Rosa; Eugenia Guida; Ambra Colopi; Sara Caratelli; Francesca De Paolis; Angela Gallo; Carlo Cenciarelli; Giuseppe Sconocchia; Susanna Dolci; Valeriana Cesarini

doi:10.1016/j.mad.2023.111807

Contribution of A-to-I RNA editing, M6A RNA Methylation, and Alternative Splicing to physiological brain aging and neurodegenerative diseases

Mech Ageing Dev. 2023 Jun:212:111807. doi: 10.1016/j.mad.2023.111807. Epub 2023 Apr 5.

Affiliations

¹ Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy. Electronic address: valentina.tassinari@uniroma2.it.
² Division of Neuroscience, Department of Psychology, Sapienza University of Rome, Rome, Italy; European Center for Brain Research, IRCCS Fondazione Santa Lucia, Rome, Italy.
³ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
⁴ Department of Biomedicine, Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy.
⁵ RNA Editing Lab., Oncohaematology Department, Cellular and Gene Therapy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ Department of Biomedicine, Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy. Electronic address: valeriana.cesarini@ift.cnr.it.

PMID: 37023929
DOI: 10.1016/j.mad.2023.111807

Abstract

Aging is a physiological and progressive phenomenon in all organisms' life cycle, characterized by the accumulation of degenerative processes triggered by several alterations within molecular pathways. These changes compromise cell fate, resulting in the loss of functions in tissues throughout the body, including the brain. Physiological brain aging has been linked to structural and functional alterations, as well as to an increased risk of neurodegenerative diseases. Post-transcriptional RNA modifications modulate mRNA coding properties, stability, translatability, expanding the coding capacity of the genome, and are involved in all cellular processes. Among mRNA post-transcriptional modifications, the A-to-I RNA editing, m6A RNA Methylation and Alternative Splicing play a critical role in all the phases of a neuronal cell life cycle and alterations in their mechanisms of action significantly contribute to aging and neurodegeneration. Here we review our current understanding of the contribution of A-to-I RNA editing, m6A RNA Methylation, and Alternative Splicing to physiological brain aging process and neurodegenerative diseases.

Keywords: A-to-I RNA editing; Alternative Splicing; Brain aging; M6A RNA Methylation; Neurodegenerative diseases.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics
Alternative Splicing*
Brain / metabolism
Humans
Methylation
Neurodegenerative Diseases* / genetics
Neurodegenerative Diseases* / metabolism
RNA / genetics
RNA Editing
RNA, Messenger / metabolism

Substances

RNA
RNA, Messenger