起始甲硫氨酸 tRNA 的过表达导致人上皮细胞中转录组 tRNA 表达的全面重编程和增殖增加。
Overexpression of initiator methionine tRNA leads to global reprogramming of tRNA expression and increased proliferation in human epithelial cells.
出版信息
RNA. 2013 Apr;19(4):461-6. doi: 10.1261/rna.037507.112. Epub 2013 Feb 19.
Abstract
Transfer RNAs (tRNAs) are typically considered housekeeping products with little regulatory function. However, several studies over the past 10 years have linked tRNA misregulation to cancer. We have previously reported that tRNA levels are significantly elevated in breast cancer and multiple myeloma cells. To further investigate the cellular and physiological effects of tRNA overexpression, we overexpressed tRNAi(Met) in two human breast epithelial cell lines. We then determined tRNA abundance changes and performed phenotypic characterization. Overexpression of tRNAi(Met) significantly altered the global tRNA expression profile and resulted in increased cell metabolic activity and cell proliferation. Our results extend the relevance of tRNA overexpression in human cells and underscore the complexity of cellular regulation of tRNA expression.
摘要
转移 RNA（tRNA）通常被认为是具有很少调节功能的管家产品。然而，过去 10 年来的几项研究将 tRNA 调节异常与癌症联系起来。我们之前曾报道过，乳腺癌和多发性骨髓瘤细胞中的 tRNA 水平显著升高。为了进一步研究 tRNA 过表达的细胞和生理效应，我们在两种人乳腺上皮细胞系中过表达了 tRNAi(Met)。然后，我们测定了 tRNA 的丰度变化并进行了表型特征分析。tRNAi(Met)的过表达显著改变了全局 tRNA 表达谱，并导致细胞代谢活性和细胞增殖增加。我们的结果扩展了 tRNA 过表达在人类细胞中的相关性，并强调了细胞对 tRNA 表达的调节的复杂性。
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4
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Proc Natl Acad Sci U S A. 1985 Jul;82(14):4587-91. doi: 10.1073/pnas.82.14.4587.
5
Initiation of in vivo protein synthesis with non-methionine amino acids.
Biochemistry. 1990 May 8;29(18):4263-8. doi: 10.1021/bi00470a001.
6
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7
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本文引用的文献
1
tRNA biology charges to the front.
Genes Dev. 2010 Sep 1;24(17):1832-60. doi: 10.1101/gad.1956510.
2
Profiling non-lysyl tRNAs in HIV-1.
RNA. 2010 Feb;16(2):267-73. doi: 10.1261/rna.1928110. Epub 2009 Dec 9.
3
Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses.
Nucleic Acids Res. 2010 Mar;38(5):e30. doi: 10.1093/nar/gkp1083. Epub 2009 Dec 8.
4
tRNA over-expression in breast cancer and functional consequences.
Nucleic Acids Res. 2009 Nov;37(21):7268-80. doi: 10.1093/nar/gkp787.
5
High levels of tRNA abundance and alteration of tRNA charging by bortezomib in multiple myeloma.
Biochem Biophys Res Commun. 2009 Jul 24;385(2):160-4. doi: 10.1016/j.bbrc.2009.05.031. Epub 2009 May 19.
6
Non-coding RNA production by RNA polymerase III is implicated in cancer.
Nat Rev Cancer. 2008 Dec;8(12):911-4. doi: 10.1038/nrc2539. Epub 2008 Nov 6.
7
The expanding RNA polymerase III transcriptome.
Trends Genet. 2007 Dec;23(12):614-22. doi: 10.1016/j.tig.2007.09.001. Epub 2007 Oct 30.
8
Role of a tRNA base modification and its precursors in frameshifting in eukaryotes.
J Biol Chem. 2007 Sep 7;282(36):26026-34. doi: 10.1074/jbc.M703391200. Epub 2007 Jul 9.
9
Tissue-specific differences in human transfer RNA expression.
PLoS Genet. 2006 Dec;2(12):e221. doi: 10.1371/journal.pgen.0020221. Epub 2006 Nov 13.
10
tRNA's wobble decoding of the genome: 40 years of modification.
J Mol Biol. 2007 Feb 9;366(1):1-13. doi: 10.1016/j.jmb.2006.11.046. Epub 2006 Nov 15.
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