Cargando…

Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells

The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, u...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Miao, Long, Qian, Borrie, Melinda S., Sun, Haohui, Zhang, Changlin, Yang, Han, Shi, Dingbo, Gartenberg, Marc R., Deng, Wuguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639082/
https://www.ncbi.nlm.nih.gov/pubmed/34793452
http://dx.doi.org/10.1371/journal.pgen.1009899
_version_ 1784609079240425472
author Chen, Miao
Long, Qian
Borrie, Melinda S.
Sun, Haohui
Zhang, Changlin
Yang, Han
Shi, Dingbo
Gartenberg, Marc R.
Deng, Wuguo
author_facet Chen, Miao
Long, Qian
Borrie, Melinda S.
Sun, Haohui
Zhang, Changlin
Yang, Han
Shi, Dingbo
Gartenberg, Marc R.
Deng, Wuguo
author_sort Chen, Miao
collection PubMed
description The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, using a live cell imaging strategy that visualizes nascent transcripts from a specific tRNA gene in yeast, we identified the nuclear basket proteins Mlp1 and Mlp2, two homologs of the human TPR protein, as regulators of tRNA export. TPR expression is significantly increased in lung cancer tissues and correlated with poor prognosis. Consistently, knockdown of TPR inhibits tRNA nuclear export, protein synthesis and cell growth in lung cancer cell lines. We further show that NXF1, a well-known mRNA nuclear export factor, associates with tRNAs and mediates their transport through nuclear pores. Collectively, our findings uncover a conserved mechanism that regulates nuclear export of tRNAs, which is a limiting step in protein synthesis in eukaryotes.
format Online
Article
Text
id pubmed-8639082
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-86390822021-12-03 Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells Chen, Miao Long, Qian Borrie, Melinda S. Sun, Haohui Zhang, Changlin Yang, Han Shi, Dingbo Gartenberg, Marc R. Deng, Wuguo PLoS Genet Research Article The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, using a live cell imaging strategy that visualizes nascent transcripts from a specific tRNA gene in yeast, we identified the nuclear basket proteins Mlp1 and Mlp2, two homologs of the human TPR protein, as regulators of tRNA export. TPR expression is significantly increased in lung cancer tissues and correlated with poor prognosis. Consistently, knockdown of TPR inhibits tRNA nuclear export, protein synthesis and cell growth in lung cancer cell lines. We further show that NXF1, a well-known mRNA nuclear export factor, associates with tRNAs and mediates their transport through nuclear pores. Collectively, our findings uncover a conserved mechanism that regulates nuclear export of tRNAs, which is a limiting step in protein synthesis in eukaryotes. Public Library of Science 2021-11-18 /pmc/articles/PMC8639082/ /pubmed/34793452 http://dx.doi.org/10.1371/journal.pgen.1009899 Text en © 2021 Chen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Miao
Long, Qian
Borrie, Melinda S.
Sun, Haohui
Zhang, Changlin
Yang, Han
Shi, Dingbo
Gartenberg, Marc R.
Deng, Wuguo
Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
title Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
title_full Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
title_fullStr Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
title_full_unstemmed Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
title_short Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
title_sort nucleoporin tpr promotes trna nuclear export and protein synthesis in lung cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639082/
https://www.ncbi.nlm.nih.gov/pubmed/34793452
http://dx.doi.org/10.1371/journal.pgen.1009899
work_keys_str_mv AT chenmiao nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT longqian nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT borriemelindas nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT sunhaohui nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT zhangchanglin nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT yanghan nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT shidingbo nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT gartenbergmarcr nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells
AT dengwuguo nucleoporintprpromotestrnanuclearexportandproteinsynthesisinlungcancercells