Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation

In eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5′cap structure and 3′poly(A) tail. These elements promote transla...

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Main Authors: Qi Zhao, Lorenzo Pavanello, Mark Bartlam, Gerlof Sebastiaan Winkler
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2023.1233842/full
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author Qi Zhao
Lorenzo Pavanello
Mark Bartlam
Gerlof Sebastiaan Winkler
author_facet Qi Zhao
Lorenzo Pavanello
Mark Bartlam
Gerlof Sebastiaan Winkler
author_sort Qi Zhao
collection DOAJ
description In eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5′cap structure and 3′poly(A) tail. These elements promote translation and prevent non-specific degradation. Degradation via the deadenylation-dependent 5′-3′ degradation pathway can be induced by trans-acting factors binding the mRNA, such as RNA-binding proteins recognising sequence elements and the miRNA-induced repression complex. These factors recruit the core mRNA degradation machinery that carries out the following steps: i) shortening of the poly(A) tail by the Ccr4-Not and Pan2-Pan3 poly (A)-specific nucleases (deadenylases); ii) removal of the 5′cap structure by the Dcp1-Dcp2 decapping complex that is recruited by the Lsm1-7-Pat1 complex; and iii) degradation of the mRNA body by the 5′-3′ exoribonuclease Xrn1. In this review, the biochemical function of the nucleases and accessory proteins involved in deadenylation-dependent mRNA degradation will be reviewed with a particular focus on structural aspects of the proteins and enzymes involved.
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spelling doaj.art-aaa00c34c6474f86bc96b7953a49fef92023-10-09T10:10:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-10-011410.3389/fgene.2023.12338421233842Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradationQi Zhao0Lorenzo Pavanello1Mark Bartlam2Gerlof Sebastiaan Winkler3State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai International Advanced Research Institute (Shenzhen Futian), Nankai University, Tianjin, ChinaSchool of Pharmacy, University of Nottingham, University Park, Nottingham, United KingdomState Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai International Advanced Research Institute (Shenzhen Futian), Nankai University, Tianjin, ChinaSchool of Pharmacy, University of Nottingham, University Park, Nottingham, United KingdomIn eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5′cap structure and 3′poly(A) tail. These elements promote translation and prevent non-specific degradation. Degradation via the deadenylation-dependent 5′-3′ degradation pathway can be induced by trans-acting factors binding the mRNA, such as RNA-binding proteins recognising sequence elements and the miRNA-induced repression complex. These factors recruit the core mRNA degradation machinery that carries out the following steps: i) shortening of the poly(A) tail by the Ccr4-Not and Pan2-Pan3 poly (A)-specific nucleases (deadenylases); ii) removal of the 5′cap structure by the Dcp1-Dcp2 decapping complex that is recruited by the Lsm1-7-Pat1 complex; and iii) degradation of the mRNA body by the 5′-3′ exoribonuclease Xrn1. In this review, the biochemical function of the nucleases and accessory proteins involved in deadenylation-dependent mRNA degradation will be reviewed with a particular focus on structural aspects of the proteins and enzymes involved.https://www.frontiersin.org/articles/10.3389/fgene.2023.1233842/fullRNApoly(A)gene expressionRNA degradation pathwayRNA decaynuclease
spellingShingle Qi Zhao
Lorenzo Pavanello
Mark Bartlam
Gerlof Sebastiaan Winkler
Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation
Frontiers in Genetics
RNA
poly(A)
gene expression
RNA degradation pathway
RNA decay
nuclease
title Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation
title_full Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation
title_fullStr Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation
title_full_unstemmed Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation
title_short Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation
title_sort structure and function of molecular machines involved in deadenylation dependent 5 3 mrna degradation
topic RNA
poly(A)
gene expression
RNA degradation pathway
RNA decay
nuclease
url https://www.frontiersin.org/articles/10.3389/fgene.2023.1233842/full
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AT lorenzopavanello structureandfunctionofmolecularmachinesinvolvedindeadenylationdependent53mrnadegradation
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AT gerlofsebastiaanwinkler structureandfunctionofmolecularmachinesinvolvedindeadenylationdependent53mrnadegradation