The Role of Nucleotide Composition in Premature Termination Codon Recognition

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2016 Dec 9

PMID 27927164

Citations 2

Authors

Fouad Zahdeh

Liran Carmel

Affiliations

Soon will be listed here.

Abstract

Background: It is not fully understood how a termination codon is recognized as premature (PTC) by the nonsense-mediated decay (NMD) machinery. This is particularly true for transcripts lacking an exon junction complex (EJC) along their 3' untranslated region (3'UTR), and thus degrade through the EJC-independent NMD pathway.

Results: Here, we analyzed data of transcript stability change following NMD repression and identified over 200 EJC-independent NMD-targets. We examined many features characterizing these transcripts, and compared them to NMD-insensitive transcripts, as well as to a group of transcripts that are destabilized following NMD repression (destabilized transcripts).

Conclusions: We found that none of the known NMD-triggering features, such as the presence of upstream open reading frames, significantly characterizes EJC-independent NMD-targets. Instead, we saw that NMD-targets are strongly enriched with G nucleotides upstream of the termination codon, and even more so along their 3'UTR. We suggest that high G content around the termination codon impedes translation termination as a result of mRNA folding, thus triggering NMD. We also suggest that high G content in the 3'UTR helps to activate NMD by allowing for the accumulation of UPF1, or other NMD-promoting proteins, along the 3'UTR.

Citing Articles

Nucleotide composition affects codon usage toward the 3'-end.

Zahdeh F, Carmel L PLoS One. 2019; 14(12):e0225633.

PMID: 31800603 PMC: 6892556. DOI: 10.1371/journal.pone.0225633.

Upf proteins: highly conserved factors involved in nonsense mRNA mediated decay.

Gupta P, Li Y Mol Biol Rep. 2017; 45(1):39-55.

PMID: 29282598 DOI: 10.1007/s11033-017-4139-7.

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