Abstract
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.
Highlights
Protein synthesis levels are tightly controlled to match the demands of cell growth
Amino acids are the building blocks for proteins, and each is carried to ribosomes for protein synthesis by its own specific transport RNAs
Our previous study discovered that transport RNAs (tRNAs) genes in yeast associate with Nuclear pore complexes (NPCs) to coordinate tRNA synthesis with nuclear export
Summary
Protein synthesis levels are tightly controlled to match the demands of cell growth. The demand for increased protein synthesis is greatest during the uncontrolled proliferation of cancer cells. Differences in transcription of a subset of tRNA genes appear to drive the differences in tRNA content between cancerous and differentiated cells [3]. A causal link between tRNA levels and cancer was suggested with the demonstration that artificial overexpression of the initiator methionine tRNA (tRNAiMet) promoted cell growth [4]. A more recent study found that tRNAGlu(UUC) and tRNAArg(CCG) were upregulated in breast cancer cells, and enhanced the stability as well as translation of mRNA transcripts enriched for their codons, shifting the cellular proteomics to a pro-metastatic state [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
