Open AccessNucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
Author(s) -
Miao Chen,
Long Qian,
Melinda S. Borrie,
Haohui Sun,
Changlin Zhang,
Han Yang,
Dingbo Shi,
Marc R. Gartenberg,
Wuguo Deng
Publication year - 2021
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009899
Subject(s) - nucleoporin , nuclear export signal , biology , nuclear pore , gene knockdown , nuclear transport , nuclear protein , protein biosynthesis , transfer rna , microbiology and biotechnology , messenger rna , cytoplasm , cell growth , eif4ebp1 , cancer cell , cell , rna , cell nucleus , gene , biochemistry , cancer , genetics , translation (biology) , transcription factor
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.