4.6 Review

3′-End Processing of Eukaryotic mRNA: Machinery, Regulation, and Impact on Gene Expression

Journal

ANNUAL REVIEW OF BIOCHEMISTRY
Volume 92, Issue -, Pages 199-225

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-biochem-052521-012445

Keywords

pre-mRNA processing; endonuclease; polyadenylation; poly(A) tail; polymerase; transcription

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The formation of the 3' end of a eukaryotic mRNA is a crucial step in mRNA maturation. Protein factors such as CPSF and CPF are responsible for cleaving the pre-mRNA, adding a poly(A) tail, and regulating transcription. The selection of the cleavage site and the length of the poly(A) tail play important roles in mRNA translation, stability, and localization.
Formation of the 3' end of a eukaryoticmRNAis a key step in the production of a mature transcript. This process is mediated by a number of protein factors that cleave the pre-mRNA, add a poly(A) tail, and regulate transcription by protein dephosphorylation. Cleavage and polyadenylation specificity factor (CPSF) in humans, or cleavage and polyadenylation factor (CPF) in yeast, coordinates these enzymatic activities with each other, with RNA recognition, and with transcription. The site of pre-mRNA cleavage can strongly influence the translation, stability, and localization of the mRNA. Hence, cleavage site selection is highly regulated. The length of the poly(A) tail is also controlled to ensure that every transcript has a similar tail when it is exported from the nucleus. In this review, we summarize new mechanistic in-sights intomRNA3' -end processing obtained through structural studies and biochemical reconstitution and outline outstanding questions in the field.

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