Driving Chromatin Organisation through N6-methyladenosine Modification of RNA: What Do We Know and What Lies Ahead?

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.

Recent advances in the plant epitranscriptome

“…Besides pre-mRNA maturation, accumulating evidence suggests that m 6 A exerts important roles in regulating chromatin accessibility and transcription in mammalian cells [ 150 , 151 ], whereas the similar evidence has just begun to emerge in plants. m 6 A affects dynamics of FCA nuclear condensates, further influencing the DNA:RNA hybrid (R-loop) formation at the COOLAIR locus in Arabidopsis [ 78 ], which indicates a possible role of m 6 A in chromatin regulation.…”

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

“…Therefore, the depletion of SAFB can significantly elevate L1 retrotransposition activity, but knockdown of “writers” and “readers” will impede the process. Furthermore, the depletion of m 6 A “writers” METTL3, METTL14, and ZC3H13 or “reader” YTHDC1 will reduce the levels of the evolutionarily young intronic L1s that are marked by m 6 A [ 775 , 777 ].…”

Copper‐Free Click Chemistry‐Mediated Assembly of Single Quantum Dot Nanosensor for Accurately Monitoring Locus‐Specific m6A in Cancer Cells†

“…Alternatively, the combination of immunoprecipitation with sequencing has been applied for m 6 A detection. [ 17 ] Typical examples include chromatin immunoprecipitation‐based sequencing [ 18 ] and methylated RNA immunoprecipitation‐based sequencing, [ 19‐20 ] but these methods involve the expensive sequencing instruments, tedious operation and RNA purification process, greatly limiting their practical applications. Ligation detection reaction (LDR) is a unique technique in which DNA ligase can successfully ligate two primer probes that have been perfectly hybridized to adjacent position of template, [ 21‐22 ] and it can achieve linear signal amplification through repeating reactions of denaturation, annealing, and ligation.…”