The canonical UPF1-dependent nonsense-mediated mRNA decay is inhibited in transcripts carrying a short open reading frame independent of sequence context

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Silva, AL (Author) Other; Pereira, FJC (Author) Other; Morgado, A (Author) Other; Kong, J (Author) Other; Martins, R (Author) Other; Faustino, P (Author) Other; Liebhaber, SA (Author) Other; Romao, L (Author) Other

Journal

Title: RNA

Vol. 12

Pages: 2160-2170

ISSN: 1355-8382

Publisher: Cold Spring Harbor Laboratory Press

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 31 Citations

Other information

Authenticus ID: P-004-FYR

DOI: 10.1261/rna.201406

Abstract (EN): 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., beta 15) 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11