Abstract
Alternative polyadenylation (APA) is a widespread and conserved regulatory mechanism that generates diverse 3′ ends on mRNA. APA patterns are often tissue specific and play an important role in cellular processes such as cell proliferation, differentiation, and response to stress. Many APA sites are found in 3′ UTRs, generating mRNA isoforms with different 3′ UTR contents. These alternate 3′ UTR isoforms can change how the transcript is regulated, affecting its stability and translation. Since the subcellular localization of a transcript is often regulated by 3′ UTR sequences, this implies that APA can also change transcript location. However, this connection between APA and RNA localization has only recently been explored. In this review, we discuss the role of APA in mRNA localization across distinct subcellular compartments. We also discuss current challenges and future advancements that will aid our understanding of how APA affects RNA localization and molecular mechanisms that drive these processes.
Highlights
Co-transcriptional maturation of pre-mRNA involves three steps - capping, splicing, and formation of a 3′ end by cleavage and addition of a poly(A) tail
The core 3′-end processing machinery is comprised of four main complexes: cleavage and polyadenylation specificity factor (CPSF), cleavage factor I (CFIm), cleavage factor II (CFIIm), and Alternative Polyadenylation and RNA Localization cleavage stimulation factor (CstF) (Shi et al, 2009)
Since alternative polyadenylation (APA) generates mRNA isoforms with different 3′ UTRs, which in turn are known to regulate RNA localization, these mRNA isoforms resulting from long term potentiation (LTP) induction may localize to distinct subcellular compartments and contribute to temporal regulation
Summary
Many APA sites are found in 3′ UTRs, generating mRNA isoforms with different 3′ UTR contents. These alternate 3′ UTR isoforms can change how the transcript is regulated, affecting its stability and translation. Since the subcellular localization of a transcript is often regulated by 3′ UTR sequences, this implies that APA can change transcript location. This connection between APA and RNA localization has only recently been explored. We discuss current challenges and future advancements that will aid our understanding of how APA affects RNA localization and molecular mechanisms that drive these processes
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