Abstract
In recent years, there has been an increase in research efforts surrounding RNA modification thanks to key breakthroughs in NGS-based whole transcriptome mapping methods. More than 100 modifications have been reported in RNAs, and some have been mapped at single-nucleotide resolution in the mammalian transcriptome. This has opened new research avenues in fields such as neurobiology, developmental biology, and oncology, among others. To date, we know that the RNA modification machinery finely tunes many diverse mechanisms involved in RNA processing and translation to regulate gene expression. However, it appears obvious to the research community that we have only just begun the process of understanding the several functions of the dynamic web of RNA modification, or the “epitranscriptome”. To expand the data generated so far, recently published studies revealed a dual role for N6-methyladenosine (m6A), the most abundant mRNA modification, in driving both chromatin dynamics and transcriptional output. These studies showed that the m6A-modified, chromatin-associated RNAs could act as molecular docks, recruiting histone modification proteins and thus contributing to the regulation of local chromatin structure. Here, we review these latest exciting findings and outline outstanding research questions whose answers will help to elucidate the biological relevance of the m6A modification of chromatin-associated RNAs in mammalian cells.
Highlights
Consiglio Nazionale delle Ricerche, Istituto di Tecnologie Biomediche, Via Fratelli Cervi 93, Istituto Nazionale di Genetica Molecolare, Via Francesco Sforza 35, 20122 Milano, Italy
To expand the data generated so far, recently published studies revealed a dual role for N6-methyladenosine (m6A), the most abundant mRNA
Modification, in driving both chromatin dynamics and transcriptional output. These studies showed that the m6A-modified, chromatin-associated RNAs could act as molecular docks, recruiting histone modification proteins and contributing to the regulation of local chromatin structure
Summary
More than 100 RNA modifications have been reported in the transcriptome of organisms spanning from archaea to eukaryotes [1]. These chemical alterations of RNA nucleotides expand the properties of a given RNA sequence, affecting its function [2]; the precise effect of each modification on distinct RNAs and the consequences on genome function are still the subjects of intensive research. RNA modifications appear dynamically regulated, primarily as a form of adaptation to stress. The depletion of the enzymes belonging to the RNA modification machinery shed partial light on the biological function of a few of these modifications, and genetic studies uncovered a robust association between mutations of RNA modifying enzymes, developmental defects [5], and cancer [6].
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