The role of nucleotide composition in premature termination codon recognition

Fouad Zahdeh, Liran Carmel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageAmerican English
Article number519
JournalBMC Bioinformatics
Volume17
Issue number1
DOIs
StatePublished - 7 Dec 2016

Bibliographical note

Publisher Copyright:
© 2016 The Author(s).

Keywords

  • EJC-independent NMD
  • Exon junction complex (EJC)
  • NMD-triggering features
  • Nonsense-mediated decay (NMD)
  • RNA secondary structure
  • Stop codon GC content
  • Stop codon nucleotide composition
  • Transcription termination

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