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Cited by 157RNA Research and SplicingRNA and protein synthesis mechanismsRNA regulation and disease

Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

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Ge, Zhiyun, Quek, Bao Lin, Beemon, Karen L, Hogg, J Robert·2016·eLife
DOI 10.7554/elife.11155PMC PMC4764554
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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.

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Cited by

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Authors
Ge, Z., Quek, B. L., Beemon, K. L., & Hogg, J. R.
Affiliations
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
Corresponding author
Hogg, J Robert
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2016-01-08
Volume
5
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.11155
PMC
PMC4764554
OpenAlex
W2227690477
Cited by
157
References
4
Citations by year
2026: 11 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 14 · 2021: 11 · 2020: 20 · 2019: 16 · 2018: 23 · 2017: 10 · 2016: 13
FWCI
10.74
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (P50 GM103297)
  • National Cancer Institute (RO1 CA048746)
  • National Heart, Lung, and Blood Institute (Intramural Research Program)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
PTBP1, nonsense-mediated mRNA decay, 3' untranslated region, UPF1, stop codon recognition, mRNA quality control
MeSH terms
Binding Sites, Gene Expression Regulation, Humans, RNA, Messenger, Trans-Activators, Sequence Analysis, RNA, Codon, Nonsense, RNA Helicases, 3' Untranslated Regions, Gene Expression Profiling, Heterogeneous-Nuclear Ribonucleoproteins, Polypyrimidine Tract-Binding Protein, Nonsense Mediated mRNA Decay

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