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 proc...
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doaj-15cfc0dd12b649e9b22a1d826674caab2021-05-05T00:12:29ZengeLife Sciences Publications LtdeLife2050-084X2016-01-01510.7554/eLife.11155Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathwayZhiyun Ge0Bao Lin Quek1https://orcid.org/0000-0001-7306-3908Karen L Beemon2J Robert Hogg3https://orcid.org/0000-0001-5729-5135Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United StatesDepartment of Biology, Johns Hopkins University, Baltimore, United StatesDepartment of Biology, Johns Hopkins University, Baltimore, United StatesBiochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United StatesThe 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.https://elifesciences.org/articles/11155PTBP1Rous sarcoma virusretrovirusnonsense-mediated mRNA decay3'UTR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhiyun Ge Bao Lin Quek Karen L Beemon J Robert Hogg |
spellingShingle |
Zhiyun Ge Bao Lin Quek Karen L Beemon J Robert Hogg Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway eLife PTBP1 Rous sarcoma virus retrovirus nonsense-mediated mRNA decay 3'UTR |
author_facet |
Zhiyun Ge Bao Lin Quek Karen L Beemon J Robert Hogg |
author_sort |
Zhiyun Ge |
title |
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway |
title_short |
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway |
title_full |
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway |
title_fullStr |
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway |
title_full_unstemmed |
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway |
title_sort |
polypyrimidine tract binding protein 1 protects mrnas from recognition by the nonsense-mediated mrna decay pathway |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2016-01-01 |
description |
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. |
topic |
PTBP1 Rous sarcoma virus retrovirus nonsense-mediated mRNA decay 3'UTR |
url |
https://elifesciences.org/articles/11155 |
work_keys_str_mv |
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