Regulation of Gene Expression by m6Am RNA Modification

The field of RNA modification, also referred to as "epitranscriptomics," is gaining more and more interest from the scientific community. More than 160 chemical modifications have been identified in RNA molecules, but the functional significance of most of them still needs to be clarified. In this review, we discuss the role of N⁶,2'-O-dimethyladenosine (m⁶A_m) in gene expression regulation. m⁶A_m is present in the first transcribed nucleotide close to the cap in many mRNAs and snRNAs in mammals and as internal modification in the snRNA U2. The writer and eraser proteins for these modifications have been recently identified and their deletions have been utilized to understand their contributions in gene expression regulation. While the role of U2 snRNA-m⁶A_m in splicing regulation has been reported by different independent studies, conflicting data were found for the role of cap-associated m⁶A_m in mRNA stability and translation. However, despite the open debate on the role of m⁶A_m in mRNA expression, the modulation of regulators produced promising results in cancer cells. We believe that the investigation on m⁶A_m will continue to yield relevant results in the future.