A Study of Post-transcriptional m6A Modification. Tang et al.

Here, we develop 4sU-m6A-level and isoform-characterization sequencing (4sU-m6A-LAIC-seq) and 4sU-GLORI, designed to quantify the m6A levels for both newly synthesized and steady-state RNAs at transcript and single-base-resolution levels, respectively, which enable dissecting the relationship between m6A modification and alternative RNA polyadenylation. Unexpectedly, our results show that many m6A addition events occur post-transcriptionally, especially on transcripts with high m6A levels. Importantly, we find higher levels of m6A on shorter 3′UTR isoforms, which likely result from sequential polyadenylation of longer 3′UTR isoforms with prolonged nuclear dwelling time. Therefore, m6A modification can also take place post-transcriptionally to intimately couple with other key RNA metabolism processes to establish and dynamically regulate the epi-transcriptomics in mammalian cells. Please refer to the manuscript titled "Nuclear Retention Coupled with Sequential Polyadenylation Dictates Post-transcriptional m6A Modification in the Nucleus" for more details.