title: The role of nucleotide composition in premature termination codon recognition.
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.
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.|Hereditary Research Lab, Life Sciences Department, Bethlehem University, Bethlehem, Palestine.
authors.forename: Fouad
authors.initials: F
authors.lastname: Zahdeh
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel. liran.carmel@huji.ac.il.
authors.forename: Liran
authors.identifier: http://orcid.org/0000-0003-0225-8550
authors.initials: L
authors.lastname: Carmel
mesh_terms: D020413:3' Untranslated Regions; D001482:Base Composition; D018389:Codon, Nonsense; D018388:Codon, Terminator; D005091:Exons; D006801:Humans; D059365:Nonsense Mediated mRNA Decay; D009711:Nucleotides / Q000032:analysis; D016366:Open Reading Frames; D010443:Peptide Chain Termination, Translational; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry
chemical_list: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D018388:Codon, Terminator; D009711:Nucleotides; D012333:RNA, Messenger
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