TY - JOUR
T1 - Global analysis of tRNA and translation factor expression reveals a dynamic landscape of translational regulation in human cancers
AU - Zhang, Zhao
AU - Ye, Youqiong
AU - Gong, Jing
AU - Ruan, Hang
AU - Liu, Chun Jie
AU - Xiang, Yu
AU - Cai, Chunyan
AU - Guo, An Yuan
AU - Ling, Jiqiang
AU - Diao, Lixia
AU - Weinstein, John N.
AU - Han, Leng
N1 - Funding Information:
We gratefully acknowledge contributions from TCGA Research Network. This work was supported by Cancer Prevention and Research Institute of Texas (RR150085 to L.H.); UTHealth Innovation for Cancer Prevention Research Training Program Post-doctoral Fellowship (Cancer Prevention and Research Institute of Texas, RP160015); National Institute of Health (NIGMS R01GM115431 to J.L.); China Scholarship Council (201606160058 to C.-J.L.); National Natural Science Foundation of China (31771458 to A.G.). We thank LeeAnn Chastain for editorial assistance.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The protein translational system, including transfer RNAs (tRNAs) and several categories of enzymes, plays a key role in regulating cell proliferation. Translation dysregulation also contributes to cancer development, though relatively little is known about the changes that occur to the translational system in cancer. Here, we present global analyses of tRNAs and three categories of enzymes involved in translational regulation in ~10,000 cancer patients across 31 cancer types from The Cancer Genome Atlas. By analyzing the expression levels of tRNAs at the gene, codon, and amino acid levels, we identified unequal alterations in tRNA expression, likely due to the uneven distribution of tRNAs decoding different codons. We find that overexpression of tRNAs recognizing codons with a low observed-over-expected ratio may overcome the translational bottleneck in tumorigenesis. We further observed overall overexpression and amplification of tRNA modification enzymes, aminoacyl-tRNA synthetases, and translation factors, which may play synergistic roles with overexpression of tRNAs to activate the translational systems across multiple cancer types.
AB - The protein translational system, including transfer RNAs (tRNAs) and several categories of enzymes, plays a key role in regulating cell proliferation. Translation dysregulation also contributes to cancer development, though relatively little is known about the changes that occur to the translational system in cancer. Here, we present global analyses of tRNAs and three categories of enzymes involved in translational regulation in ~10,000 cancer patients across 31 cancer types from The Cancer Genome Atlas. By analyzing the expression levels of tRNAs at the gene, codon, and amino acid levels, we identified unequal alterations in tRNA expression, likely due to the uneven distribution of tRNAs decoding different codons. We find that overexpression of tRNAs recognizing codons with a low observed-over-expected ratio may overcome the translational bottleneck in tumorigenesis. We further observed overall overexpression and amplification of tRNA modification enzymes, aminoacyl-tRNA synthetases, and translation factors, which may play synergistic roles with overexpression of tRNAs to activate the translational systems across multiple cancer types.
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U2 - 10.1038/s42003-018-0239-8
DO - 10.1038/s42003-018-0239-8
M3 - Article
C2 - 30588513
AN - SCOPUS:85067676984
SN - 2399-3642
VL - 1
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 234
ER -