Single-base mapping of m6A in lncRNAs reveals a distinct landscape linked to transposable elements and RNA processing

Abstract

N6-methyladenosine (m6A) is the most abundant internal RNA modification with established roles in mRNA metabolism. Although m6A has been characterized in several well-known long noncoding RNAs (lncRNAs), its transcriptome-wide landscape and roles remain poorly understood. Here, we characterized the m6A landscape of lncRNAs at single-base resolution, identified m6A deposition-associated features, and investigated potential roles of m6A in lncRNA processing. Unlike in mRNAs, m6A sites are broadly distributed along lncRNAs. We further found that these differences in m6A patterns between lncRNAs and mRNAs may reflect contributions from transposable element-derived sequence to motif availability and local RNA structure, together with splicing-related constraints on m6A deposition near exon junctions. Additionally, m6A may be relevant to the regulation of lncRNA polyadenylation. Together, these findings define the single-base-resolution m6A landscape in lncRNAs, and connect lncRNA methylation to transposable elements, RNA structure, splicing, and polyadenylation. This study broadens our understanding of m6A in the lncRNA epitranscriptome.