Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9

Newman Zachary R.; Young Janet M.; Ingolia Nicholas T.Barton Gregory M.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9

【24h】

Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9

机译：Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

The innate immune system detects diverse microbial species with a limited repertoire of immune receptors that recognize nucleic acids. The cost of this immune surveillance strategy is the potential for inappropriate recognition of self-derived nucleic acids and subsequent autoimmune disease. The relative expression of two closely related receptors, Toll-like receptor (TLR) 7 and TLR9, is balanced to allow recognition of microbial nucleic acids while limiting recognition of self-derived nucleic acids. Situations that tilt this balance toward TLR7 promote inappropriate responses, including autoimmunity; therefore, tight control of expression is critical for proper homeostasis. Here we report that differences in codon bias limit TLR7 expression relative to TLR9. Codon optimization of Tlr7 increases protein levels as well as responses to ligands, but, unexpectedly, these changes only modestly affect translation. Instead, we find that much of the benefit attributed to codon optimization is actually the result of enhanced transcription. Our findings, together with other recent examples, challenge the dogma that codon optimization primarily increases translation. We propose that suboptimal codon bias, which correlates with low guanine-cytosine (GC) content, limits transcription of certain genes. This mechanism may establish low levels of proteins whose overexpression leads to particularly deleterious effects, such as TLR7.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2016年第10期|E1362-E1371|共10页
作者
Newman Zachary R.; Young Janet M.; Ingolia Nicholas T.Barton Gregory M.;
展开▼
作者单位

Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, 229 Stanley Hall, Berkeley, CA 94720 USA;

Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA;

Univ Calif Berkeley, Dept Mol & Cell Biol, Div Biochem Biophys & Struct Biol, 229 Stanley Hall, Berkeley, CA 94720 USA;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Toll-like receptors; codon bias; GC content; TLR7; TLR9;

Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9

摘要

著录项

相关主题

期刊订阅