Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.
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.
['Ge|Zhiyun|Z|', 'Quek|Bao Lin|BL|http://orcid.org/0000-0001-7306-3908', 'Beemon|Karen L|KL|', 'Hogg|J Robert|JR|http://orcid.org/0000-0001-5729-5135']
D020413:3' Untranslated Regions D001665:Binding Sites D018389:Codon, Nonsense D020869:Gene Expression Profiling D005786:Gene Expression Regulation D034441:Heterogeneous-Nuclear Ribonucleoproteins D006801:Humans D059365:Nonsense Mediated mRNA Decay D038941:Polypyrimidine Tract-Binding Protein D020365:RNA Helicases D012333:RNA, Messenger D017423:Sequence Analysis, RNA D015534:Trans-Activators
nonsense-mediated mRNA decay 3'UTR PTBP1 human Rous sarcoma virus biochemistry chicken infectious disease microbiology retrovirus