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

Author:

Mailliot Justine1ORCID,Vivoli-Vega Mirella1ORCID,Schaffitzel Christiane12ORCID

Affiliation:

1. School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, U.K.

2. Bristol Synthetic Biology Centre BrisSynBio, 24 Tyndall Ave, Bristol BS8 1TQ, U.K.

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.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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