LncRNAs and Chromatin Modifications Pattern m(6)A Methylation at the Untranslated Regions of mRNAs

New roles for RNA in mediating gene expression are being discovered at an alarming rate. A broad array of pathways control patterning of N(6)-methyladenosine (m(6)A) methylation on RNA transcripts. This review comprehensively discusses long non-coding RNAs (lncRNAs) as an additional dynamic regulator of m(6)A methylation, with a focus on the untranslated regions (UTRs) of mRNAs. Although there is extensive literature describing m(6)A modification of lncRNA, the function of lncRNA in guiding m(6)A writers has not been thoroughly explored. The independent control of lncRNA expression, its heterogeneous roles in RNA metabolism, and its interactions with epigenetic machinery, alludes to their potential in dynamic patterning of m(6)A methylation. While epigenetic regulation by histone modification of H3K36me3 has been demonstrated to pattern RNA m(6)A methylation, these modifications were specific to the coding and 3′UTR regions. However, there are observations that 5′UTR m(6)A is distinct from that of the coding and 3′UTR regions, and substantial evidence supports the active regulation of 5′UTR m(6)A methylation. Consequently, two potential mechanisms in patterning the UTRs m(6)A methylation are discussed; (1) Anti-sense lncRNA (AS-lncRNA) can either bind directly to the UTR, or (2) act indirectly via recruitment of chromatin-modifying complexes to pattern m(6)A. Both pathways can guide the m(6)A writer complex, facilitate m(6)A methylation and modulate protein translation. Findings in the lncRNA-histone-m(6)A axis could potentially contribute to the discovery of new functions of lncRNAs and clarify lncRNA-m(6)A findings in translational medicine.