Arginine limitation drives a directed codon-dependent DNA sequence evolution response in colorectal cancer cells.
Arginine limitation drives a directed codon-dependent DNA sequence evolution response in colorectal cancer cells.
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DOI：
10.1126/sciadv.ade9120
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发表时间：
2023-01-06
期刊：
影响因子：
13.6
通讯作者：
Tavazoie, Sohail F.
中科院分区：
文献类型：
--
作者：
Hsu, Dennis J.;Gao, Jenny;Yamaguchi, Norihiro;Pinzaru, Alexandra;Wu, Qiushuang;Mandayam, Nandan;Liberti, Maria;Heissel, Soren;Alwaseem, Hanan;Tavazoie, Saeed;Tavazoie, Sohail F.
不同生物体对特定密码子的利用不同。癌症代表了理解DNA序列进化的模型，并可能揭示密码子进化背后的因果因素。我们发现，在人类癌症中，精氨酸密码子经常突变为其他密码子。此外，精氨酸限制-肿瘤微环境的一个特征-足以诱导人结肠癌细胞中精氨酸密码子转换突变。这种DNA密码子转换事件编码具有精氨酸残基取代的突变蛋白。从机制上讲，精氨酸限制导致精氨酸转移RNA的快速减少和核糖体在精氨酸密码子上的停滞。这种对精氨酸密码子翻译的选择性压力诱导了适应性蛋白质组学向含低精氨酸密码子的基因（包括特定氨基酸转运蛋白）的转变，并导致突变进化远离精氨酸饥饿期间发生的精氨酸密码子减少翻译瓶颈。因此，特定氨基酸的环境可用性可以影响DNA序列进化远离其同源密码子并产生改变的蛋白质。细胞外精氨酸限制导致突变远离精氨酸密码子，有利于低精氨酸蛋白质翻译。
Utilization of specific codons varies between organisms. Cancer represents a model for understanding DNA sequence evolution and could reveal causal factors underlying codon evolution. We found that across human cancer, arginine codons are frequently mutated to other codons. Moreover, arginine limitation—a feature of tumor microenvironments—is sufficient to induce arginine codon–switching mutations in human colon cancer cells. Such DNA codon switching events encode mutant proteins with arginine residue substitutions. Mechanistically, arginine limitation caused rapid reduction of arginine transfer RNAs and the stalling of ribosomes over arginine codons. Such selective pressure against arginine codon translation induced an adaptive proteomic shift toward low-arginine codon–containing genes, including specific amino acid transporters, and caused mutational evolution away from arginine codons—reducing translational bottlenecks that occurred during arginine starvation. Thus, environmental availability of a specific amino acid can influence DNA sequence evolution away from its cognate codons and generate altered proteins. Extracellular arginine limitation causes mutation away from arginine codons and favors low-arginine protein translation.
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影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
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Noushmehr H
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4
作者：
Alexandrov, Ludmil B.;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
64.5
作者：
Gingold, Hila;Tehler, Disa;Pilpel, Yitzhak
通讯作者：
Pilpel, Yitzhak
影响因子：
16
作者：
Goodarzi H;Elemento O;Tavazoie S
通讯作者：
Tavazoie S