Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation

During their synthesis in the cell nucleus, most eukaryotic mRNAs undergo a two‐step 3′‐end processing reaction in which the pre‐mRNA is cleaved and released from the transcribing RNA polymerase II and a polyadenosine (poly(A)) tail is added to the newly formed 3′‐end. These biochemical reactions mi...

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Main Authors: Juan B. Rodríguez‐Molina, Matti Turtola
Format: Article
Language:English
Published: Wiley 2023-07-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13528
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author Juan B. Rodríguez‐Molina
Matti Turtola
author_facet Juan B. Rodríguez‐Molina
Matti Turtola
author_sort Juan B. Rodríguez‐Molina
collection DOAJ
description During their synthesis in the cell nucleus, most eukaryotic mRNAs undergo a two‐step 3′‐end processing reaction in which the pre‐mRNA is cleaved and released from the transcribing RNA polymerase II and a polyadenosine (poly(A)) tail is added to the newly formed 3′‐end. These biochemical reactions might appear simple at first sight (endonucleolytic RNA cleavage and synthesis of a homopolymeric tail), but their catalysis requires a multi‐faceted enzymatic machinery, the cleavage and polyadenylation complex (CPAC), which is composed of more than 20 individual protein subunits. The activity of CPAC is further orchestrated by Poly(A) Binding Proteins (PABPs), which decorate the poly(A) tail during its synthesis and guide the mRNA through subsequent gene expression steps. Here, we review the structure, molecular mechanism, and regulation of eukaryotic mRNA 3′‐end processing machineries with a focus on the polyadenylation step. We concentrate on the CPAC and PABPs from mammals and the budding yeast, Saccharomyces cerevisiae, because these systems are the best‐characterized at present. Comparison of their functions provides valuable insights into the principles of mRNA 3′‐end processing.
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spelling doaj.art-b14c7bcfd80d45ad853a6d801ec519902023-07-03T07:24:35ZengWileyFEBS Open Bio2211-54632023-07-011371140115310.1002/2211-5463.13528Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylationJuan B. Rodríguez‐Molina0Matti Turtola1MRC Laboratory of Molecular Biology Cambridge UKDepartment of Life Technologies University of Turku FinlandDuring their synthesis in the cell nucleus, most eukaryotic mRNAs undergo a two‐step 3′‐end processing reaction in which the pre‐mRNA is cleaved and released from the transcribing RNA polymerase II and a polyadenosine (poly(A)) tail is added to the newly formed 3′‐end. These biochemical reactions might appear simple at first sight (endonucleolytic RNA cleavage and synthesis of a homopolymeric tail), but their catalysis requires a multi‐faceted enzymatic machinery, the cleavage and polyadenylation complex (CPAC), which is composed of more than 20 individual protein subunits. The activity of CPAC is further orchestrated by Poly(A) Binding Proteins (PABPs), which decorate the poly(A) tail during its synthesis and guide the mRNA through subsequent gene expression steps. Here, we review the structure, molecular mechanism, and regulation of eukaryotic mRNA 3′‐end processing machineries with a focus on the polyadenylation step. We concentrate on the CPAC and PABPs from mammals and the budding yeast, Saccharomyces cerevisiae, because these systems are the best‐characterized at present. Comparison of their functions provides valuable insights into the principles of mRNA 3′‐end processing.https://doi.org/10.1002/2211-5463.13528cleavage and polyadenylation factorcleavage factormRNA 3'‐end processingpoly(A) binding proteinpoly(A) tail lengthpolyadenylation
spellingShingle Juan B. Rodríguez‐Molina
Matti Turtola
Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation
FEBS Open Bio
cleavage and polyadenylation factor
cleavage factor
mRNA 3'‐end processing
poly(A) binding protein
poly(A) tail length
polyadenylation
title Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation
title_full Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation
title_fullStr Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation
title_full_unstemmed Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation
title_short Birth of a poly(A) tail: mechanisms and control of mRNA polyadenylation
title_sort birth of a poly a tail mechanisms and control of mrna polyadenylation
topic cleavage and polyadenylation factor
cleavage factor
mRNA 3'‐end processing
poly(A) binding protein
poly(A) tail length
polyadenylation
url https://doi.org/10.1002/2211-5463.13528
work_keys_str_mv AT juanbrodriguezmolina birthofapolyatailmechanismsandcontrolofmrnapolyadenylation
AT mattiturtola birthofapolyatailmechanismsandcontrolofmrnapolyadenylation