Abstract
Alternative polyadenylation (APA) represents an important mechanism for regulating isoform-specific translation efficiency, stability, and localisation. Though some progress has been made in understanding its consequences in metazoans, the role of APA in the model organism Saccharomyces cerevisiae remains a relative mystery because, despite abundant studies on the translational state of mRNA, none differentiate mRNA isoforms’ alternative 3′-end. This review discusses the implications of alternative polyadenylation in S. cerevisiae using other organisms to draw inferences. Given the foundational role that research in this yeast has played in the discovery of the mechanisms of cleavage and polyadenylation and in the drivers of APA, it is surprising that such an inference is required. However, because advances in ribosome profiling are insensitive to APA, how it impacts translation is still unclear. To bridge the gap between widespread observed APA and the discovery of any functional consequence, we also provide a review of the experimental techniques used to uncover the functional importance of 3′ UTR isoforms on translation.
Highlights
Despite the close relationship between eukaryotic mRNA and protein expression, changes to mRNA concentrations do not always correlate to changes at the protein level.The 30 untranslated region (30 UTR) of mRNA plays a key role in regulating gene expression.In particular, mRNA stability, localisation and translation are largely impacted by the many cis-regulatory elements within the 30 UTR
Though the majority of proteins that make up the yeast core cleavage and polyadenylation machinery have been identified, and much has been learnt about how alternative cleavage sites are selected [2], the role of this alternative polyadenylation (APA) remains a relative mystery
The discovery of whether changes to the length of the 30 UTR alter the translational efficiency of an mRNA transcript has been compromised by the techniques used to study the translatome
Summary
Despite the close relationship between eukaryotic mRNA and protein expression, changes to mRNA concentrations do not always correlate to changes at the protein level. MRNA isoforms produced from alternative poly(A) sites within the 30 UTR generate the same protein; they differ in the length of their 30 UTR In such cases, the longer isoform tends to have a higher potential for regulation, due to additional regulatory elements present within the extended 30 UTR. The longer isoform tends to have a higher potential for regulation, due to additional regulatory elements present within the extended 30 UTR It is clear from multiple gene-by-gene and transcriptome-wide studies that the relative concentration of the cleavage and polyadenylation factors, the rate of transcription, and chromatin architecture can influence poly(A)-choice [2,3,4,5,6]. UTR of Hip restored luciferase expression to levels seen with the shorter 3′ UTR isoform
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