Sequential Polyadenylation to Enable Alternative mRNA3' End Formation

In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3 ' end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3 ' ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3 ' UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered apparent APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism paradigms.

Automated summary

In eukaryotic cells, the coupled reaction for cleavage and polyadenylation (CPA) at the 3' end of transcripts is a key step in generating mature mRNA. Alternative polyadenylation (APA) can produce mRNA isoforms with different 3' ends, which may affect the coding sequence or 3' UTR length. Recent studies have shown that APA can occur after transcription through a mechanism called sequential APA. This mini-review focuses on these new mechanisms of post-transcriptional APA.