Alternative cleavage and polyadenylation: the long and short of it

• Alternative cleavage and polyadenylation (APA) is widespread in eukaryotes.
• APA impacts the cellular transcriptome and proteome.
• APA is dynamic under different biological conditions.
• APA is modulated by multiple mechanisms.

Cleavage and polyadenylation (C/P) of nascent transcripts is essential for maturation of the 3′ ends of most eukaryotic mRNAs. Over the past three decades, biochemical studies have elucidated the machinery responsible for the seemingly simple C/P reaction. Recent genomic analyses have indicated that most eukaryotic genes have multiple cleavage and polyadenylation sites (pAs), leading to transcript isoforms with different coding potentials and/or variable 3′ untranslated regions (UTRs). As such, alternative cleavage and polyadenylation (APA) is an important layer of gene regulation impacting mRNA metabolism. Here, we review our current understanding of APA and recent progress in this field.