The Canonical UPF1-dependent Nonsense-mediated MRNA Decay is Inhibited in Transcripts Carrying a Short Open Reading Frame Independent of Sequence Context

Overview

Journal RNA

Specialty Molecular Biology

Date 2006 Nov 2

PMID 17077274

Citations 29

Authors

Ana Luisa Silva

Francisco J C Pereira

Ana Morgado

Jian Kong

Rute Martins

Paula Faustino

Stephen A Liebhaber

Luisa Romao

Affiliations

Soon will be listed here.

Abstract

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs carrying premature translation termination codons. Generally, NMD is elicited if translation terminates >50-54 nucleotides (nt) upstream of an exon-exon junction. We have previously reported that human beta-globin mRNAs carrying 5'-proximal nonsense mutations (e.g., beta15) accumulate to normal levels, suggesting an exception to the "50-54-nt boundary rule." In the present report, we demonstrate that the strength of the UPF1-dependent NMD of mutant beta-globin mRNAs is specifically determined by the proximity of the nonsense codon to the initiation AUG. This conclusion is supported by a parallel effect of the short ORF size on NMD of nonsense-containing alpha-globin mRNAs. To determine whether the short-ORF effect on NMD response is conserved in heterologous transcripts, we assessed its effects on a set of beta-globin/triosephosphate isomerase (TPI) hybrid mRNAs and on the TPI mRNA. Our data support the conclusion that nonsense mutations resulting in a short ORF are able to circumvent the full activity of the canonical UPF1-dependent NMD pathway.

Citing Articles

Nonsense-Mediated mRNA Decay: Mechanistic Insights and Physiological Significance.

Patro I, Sahoo A, Nayak B, Das R, Majumder S, Panigrahi G Mol Biotechnol. 2023; 66(11):3077-3091.

PMID: 37930508 DOI: 10.1007/s12033-023-00927-4.

aenmd: annotating escape from nonsense-mediated decay for transcripts with protein-truncating variants.

Klonowski J, Liang Q, Coban-Akdemir Z, Lo C, Kostka D Bioinformatics. 2023; 39(9).

PMID: 37688563 PMC: 10534055. DOI: 10.1093/bioinformatics/btad556.

aenmd: Annotating escape from nonsense-mediated decay for transcripts with protein-truncating variants.

Klonowski J, Liang Q, Coban-Akdemir Z, Lo C, Kostka D bioRxiv. 2023; .

PMID: 36993377 PMC: 10055276. DOI: 10.1101/2023.03.17.533185.

Nonsense-mediated RNA decay and its bipolar function in cancer.

Nogueira G, Fernandes R, Garcia-Moreno J, Romao L Mol Cancer. 2021; 20(1):72.

PMID: 33926465 PMC: 8082775. DOI: 10.1186/s12943-021-01364-0.

Analysis of somatic microsatellite indels identifies driver events in human tumors.

Maruvka Y, Mouw K, Karlic R, Parasuraman P, Kamburov A, Polak P Nat Biotechnol. 2017; 35(10):951-959.

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