Isoform characterization of m⁶A in single cells identifies its role in RNA surveillance.

ABSTRACT: The distribution of m⁶A across various RNA isoforms and its heterogeneity within single cells are still not well understood. Here, we develop m⁶A-isoSC-seq, which employs both Oxford Nanopore long-read and Illumina short-read sequencing on the same 10x Genomics single-cell cDNA library with APOBEC1-YTH induced C-to-U mutations near m⁶A sites. Through m⁶A-isoSC-seq on a pooled sample of three cell line origins, we unveil a profound degree of m⁶A heterogeneity at both the isoform and single-cell levels. Through comparisons across single cells, we identify widespread specific m⁶A methylation on certain RNA isoforms, usually those misprocessed RNA isoforms. Compared to the coding isoforms of the same genes, the expression of hig

SUBMITTER: Ren Z 

PROVIDER: S-EPMC12219666 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature