SOX4-mediated repression of specific tRNAs inhibits proliferation of human glioblastoma cells
| Autor: | Jianjing Yang, Haoqi Ni, Ke Wu, Chao Xing, Derek K. Smith, Dongdong Huang, Chun Li Zhang, Adwait Amod Sathe, Yu Tang, Meng Lu Liu, Sishi Pan, Qichuan Zhuge |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Multidisciplinary
Brain Neoplasms TATA-Box Binding Protein Translation (biology) Biological Sciences Biology RNA polymerase III SOXC Transcription Factors Chromatin Cell biology HEK293 Cells RNA Transfer Cell Line Tumor Codon usage bias Transfer RNA Protein biosynthesis Humans Glioblastoma Transcription factor Cell Proliferation DNA Polymerase III |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1920200117 |
| Popis: | Transfer RNAs (tRNAs) are products of RNA polymerase III (Pol III) and essential for mRNA translation and ultimately cell growth and proliferation. Whether and how individual tRNA genes are specifically regulated is not clear. Here, we report that SOX4, a well-known Pol II-dependent transcription factor that is critical for neurogenesis and reprogramming of somatic cells, also directly controls, unexpectedly, the expression of a subset of tRNA genes and therefore protein synthesis and proliferation of human glioblastoma cells. Genome-wide location analysis through chromatin immunoprecipitation-sequencing uncovers specific targeting of SOX4 to a subset of tRNA genes, including those for tRNAi Met . Mechanistically, sequence-specific SOX4-binding impedes the recruitment of TATA box binding protein and Pol III to tRNA genes and thereby represses their expression. CRISPR/Cas9-mediated down-regulation of tRNAi Met greatly inhibits growth and proliferation of human glioblastoma cells. Conversely, ectopic tRNAi Met partially rescues SOX4-mediated repression of cell proliferation. Together, these results uncover a regulatory mode of individual tRNA genes to control cell behavior. Such regulation may coordinate codon usage and translation efficiency to meet the demands of diverse tissues and cell types, including cancer cells. |
| Databáze: | OpenAIRE |
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