No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors

Justine M Mailliot; Mirella Vivoli Vega; Christiane H Berger-Schaffitzel

doi:10.1042/BCJ20210556

No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors

Justine M Mailliot^*
, Mirella Vivoli Vega^*
, Christiane H Berger-Schaffitzel^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3′-untranslated region and the presence of an exon-junction complex (EJC) downstream of the stop codon. Here, we review our structural understanding of mammalian NMD factors and their functional interplay leading to a branched network of different interconnected but specialised mRNA decay pathways. We discuss recent insights into the potential impact of EJC composition on NMD pathway choice. We highlight the coexistence and function of different isoforms of up-frameshift protein 1 (UPF1) with an emphasis of their role at the endoplasmic reticulum and during stress, and the role of the paralogs UPF3B and UPF3A, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types.

Original language	English
Pages (from-to)	973-993
Number of pages	21
Journal	Biochemical Journal
Volume	479
Issue number	9
Early online date	12 Apr 2022
DOIs	https://doi.org/10.1042/BCJ20210556
Publication status	Published - 12 May 2022

Bibliographical note

Funding Information:
We would like to thank Drs. Kyle Powers, George Orriss, Sathish Yadav Kadapalakere, Lingling Sun, and Jenn-Yeu Alvin Szeto for discussing the manuscript, critical reading and helpful comments. C.S. is Investigator of the Wellcome Trust (210701/Z/18/Z). M.V.V. and C.S. acknowledge support by a Marie Sklodowska-Curie Fellowship from the EC (101024558). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

Publisher Copyright:
© 2022 The Author(s)

Research Groups and Themes

Bristol BioDesign Institute

Keywords

cryogenic electron microscopy
synthetic biology
exon-junction complexes
up-frameshift proteins
Nonsense-mediated mRNA decay
cellular stress response
X-ray crystallography
SMG proteins

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title = "No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors",

abstract = "Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3′-untranslated region and the presence of an exon-junction complex (EJC) downstream of the stop codon. Here, we review our structural understanding of mammalian NMD factors and their functional interplay leading to a branched network of different interconnected but specialised mRNA decay pathways. We discuss recent insights into the potential impact of EJC composition on NMD pathway choice. We highlight the coexistence and function of different isoforms of up-frameshift protein 1 (UPF1) with an emphasis of their role at the endoplasmic reticulum and during stress, and the role of the paralogs UPF3B and UPF3A, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types.",

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note = "Funding Information: We would like to thank Drs. Kyle Powers, George Orriss, Sathish Yadav Kadapalakere, Lingling Sun, and Jenn-Yeu Alvin Szeto for discussing the manuscript, critical reading and helpful comments. C.S. is Investigator of the Wellcome Trust (210701/Z/18/Z). M.V.V. and C.S. acknowledge support by a Marie Sklodowska-Curie Fellowship from the EC (101024558). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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doi = "10.1042/BCJ20210556",

language = "English",

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N1 - Funding Information: We would like to thank Drs. Kyle Powers, George Orriss, Sathish Yadav Kadapalakere, Lingling Sun, and Jenn-Yeu Alvin Szeto for discussing the manuscript, critical reading and helpful comments. C.S. is Investigator of the Wellcome Trust (210701/Z/18/Z). M.V.V. and C.S. acknowledge support by a Marie Sklodowska-Curie Fellowship from the EC (101024558). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: © 2022 The Author(s)

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N2 - Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3′-untranslated region and the presence of an exon-junction complex (EJC) downstream of the stop codon. Here, we review our structural understanding of mammalian NMD factors and their functional interplay leading to a branched network of different interconnected but specialised mRNA decay pathways. We discuss recent insights into the potential impact of EJC composition on NMD pathway choice. We highlight the coexistence and function of different isoforms of up-frameshift protein 1 (UPF1) with an emphasis of their role at the endoplasmic reticulum and during stress, and the role of the paralogs UPF3B and UPF3A, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types.

AB - Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3′-untranslated region and the presence of an exon-junction complex (EJC) downstream of the stop codon. Here, we review our structural understanding of mammalian NMD factors and their functional interplay leading to a branched network of different interconnected but specialised mRNA decay pathways. We discuss recent insights into the potential impact of EJC composition on NMD pathway choice. We highlight the coexistence and function of different isoforms of up-frameshift protein 1 (UPF1) with an emphasis of their role at the endoplasmic reticulum and during stress, and the role of the paralogs UPF3B and UPF3A, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types.

KW - cryogenic electron microscopy

KW - synthetic biology

KW - exon-junction complexes

KW - up-frameshift proteins

KW - Nonsense-mediated mRNA decay

KW - cellular stress response

KW - X-ray crystallography

KW - SMG proteins

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DO - 10.1042/BCJ20210556

M3 - Article (Academic Journal)

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SN - 0264-6021

VL - 479

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EP - 993

JO - Biochemical Journal

JF - Biochemical Journal

IS - 9

ER -

No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors

Abstract

Bibliographical note

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Keywords

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