Beyond simple tails: poly(A) tail-mediated RNA epigenetic regulation.

New methods are enabling comprehensive transcriptome-wide poly(A) tail analysis. Cytoplasmic dynamics involving the deadenylation and polyadenylation of poly(A) tails regulate gene expression. Non-A residues are prevalent in the 3′ ends and the internal body of poly(A) tails, where they may play crucial roles in RNA regulation. Poly(A) tails potentially encode vital epigenetic regulatory information. The poly(A) tail is an essential structural component of mRNA required for the latter's stability and translation. Recent technologies have enabled transcriptome-wide profiling of the length and composition of poly(A) tails, shedding light on their overlooked regulatory capacities. Notably, poly(A) tails contain not only adenine but also uracil, cytosine, and guanine residues. These findings strongly suggest that poly(A) tails could encode a wealth of regulatory information, similar to known reversible RNA chemical modifications. This review aims to succinctly summarize our current knowledge on the composition, dynamics, and regulatory functions of RNA poly(A) tails. Given their capacity to carry rich regulatory information beyond the genetic code, we propose the concept of 'poly(A) tail epigenetic information' as a new layer of RNA epigenetic regulation. [ABSTRACT FROM AUTHOR]