title: Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.
abstract: The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD.
authors.affiliation: Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: Bao Lin
authors.identifier: http://orcid.org/0000-0001-7306-3908
authors.initials: BL
authors.lastname: Quek
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Beemon
authors.affiliation: Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States.
authors.forename: J Robert
authors.identifier: http://orcid.org/0000-0001-5729-5135
authors.initials: JR
authors.lastname: Hogg
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D018389:Codon, Nonsense; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D059365:Nonsense Mediated mRNA Decay; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D020365:RNA Helicases; D012333:RNA, Messenger / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015534:Trans-Activators / Q000037:antagonists & inhibitors
chemical_list: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C450006:PTBP1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D038941:Polypyrimidine Tract-Binding Protein; D020365:RNA Helicases; C101828:UPF1 protein, human
keywords: 3'UTR; PTBP1; Rous sarcoma virus; biochemistry; chicken; human; infectious disease; microbiology; nonsense-mediated mRNA decay; retrovirus