PreprintCited by 249RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

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The end of the message: multiple protein–RNA interactions define the mRNA polyadenylation site

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Shi, Yongsheng, Manley, James L.·2015·Genes & Development

DOI 10.1101/gad.261974.115PMC PMC4421977

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Abstract

The key RNA sequence elements and protein factors necessary for 3′ processing of polyadenylated mRNA precursors are well known. Recent studies, however, have significantly reshaped current models for the protein–RNA interactions involved in poly(A) site recognition, painting a picture more complex than previously envisioned and also providing new insights into regulation of this important step in gene expression. Here we review the recent advances in this area and provide a perspective for future studies.

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Figure 1. (A) Schematic models showing distinct modules within CPSF. CPSF73, CPSF100, and Symplekin form a module (which we refer to as mCF) that contains the endonuclease activity. mCF may cooperate with different RNA-binding modules, such as mammalian polyadenylation specificity factor (mPSF) (Wdr33, CPSF30, Fip1, and CPSF160), for cleavage/polyadenylation of most mRNAs or with SLBP and U7 snRNP for the cleavage of histone mRNAs. (B, bottom panel) Domain structures of the CPSF subunits involved or implicated in RNA binding. The known or putative RNA-binding regions are marked with red solid or dotted underlines.CC BY-NC · PubMed Central

Figure 2. (A) CstF-dependent and potentially CstF-independent PAS recognition. In the CstF-independent model, CstF is shown in a dotted boundary to indicate that CstF may or may not be present in this complex. The scaffolding protein Symplekin plays a role in bridging CPSF–CstF complexes. (B) CFI–RNA interactions. (Top panel) CFI binds to UGUA motifs often found upstream of the AAUAAA hexamer. (Bottom panel) The CFI dimer may bind to two UGUA sequences at different PASs, thus looping out the proximal PASs. (C) The role of Rbbp6 in PAS recognition. The question mark denotes the fact that Rbbp6 may or may not directly interact with upstream AU-rich elements (AREs) or may rely on an unknown factor.CC BY-NC · PubMed Central

Figure 3. Context-dependent regulation of PAS recognition. Regulatory factors bound at different locations relative to the core PAS sequence have different effects on PAS recognition by the mRNA 3′ processing factors. Positive effects are indicated by an arrow, and negative effects are indicated by a vertical line.CC BY-NC · PubMed Central

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Authors: Shi, Y., & Manley, J. L.
Affiliations: University of California, Irvine (US)
Columbia University (US)
Corresponding author: Shi, Yongsheng
Manley, James L.
ORCID: Shi, Yongsheng
Manley, James L.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2015-05-01
Volume: 29
Issue: 9
Pages: 889-897
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.261974.115
PMC: PMC4421977
OpenAlex: W2056608604
Cited by: 249
References: 108
Citations by year: 2026: 5 · 2025: 19 · 2024: 12 · 2023: 19 · 2022: 22 · 2021: 34 · 2020: 29 · 2019: 30 · 2018: 22 · 2017: 27 · 2016: 26 · 2015: 4
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Genes & Development (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
Funders: National Institutes of Health (GM090056, CA177651)
American Cancer Society (RSG-12-186)
NIH (GM28983)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: mRNA polyadenylation, RNA-protein interactions, polyadenylation factors, 3' end processing, mRNA precursors, gene expression regulation, polyadenylation signal
MeSH terms: Gene Expression Regulation, Protein Binding, RNA Precursors, RNA, Messenger, Conserved Sequence, Amino Acid Motifs, Polyadenylation, Cleavage And Polyadenylation Specificity Factor

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The end of the message: multiple protein–RNA interactions define the mRNA polyadenylation site

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