Mechanism of trans-translation revealed by in vitro studies.
Mechanism of trans-translation revealed by in vitro studies.
复制标题
DOI：
10.3389/fmicb.2014.00065
复制
发表时间：
2014
影响因子：
5.2
通讯作者：
Muto A
中科院分区：
文献类型：
--
作者：
Himeno H;Kurita D;Muto A
tmRNA是一种细菌小RNA，其结构类似tRNA的上半部分，其3 '端接受丙氨酸，然后与EF-Tu样tRNA结合。tmRNA不缺少包括反密码子在内的三叶草结构的下半部分，而是具有作为细胞蛋白酶靶点的标签肽的短编码序列。tRNA和mRNA两种功能的精细协调促进了称为反翻译的不规则翻译：一个单一的多肽由两个mRNA分子合成。它允许在截断的mRNA上恢复翻译，产生嵌合多肽，包括由截断的mRNA衍生的c端截断多肽和由tmRNA编码的c端标记肽。反翻译促进细胞中停滞的核糖体的再循环，由此产生的c端标记多肽被细胞蛋白酶优先降解。利用体外反翻译系统的生化研究和结构研究揭示了反翻译的分子机制，在反翻译过程中，tRNA的上半部分和下半部分分别被tmRNA的tRNA样结构和tmRNA特异性结合蛋白SmpB模拟。它们不仅模仿tRNA的结构，而且模仿其在核糖体中反译过程的每一步的行为。此外，SmpB的c端尾在溶液中是非结构化的，占据了核糖体中的mRNA路径，在反翻译中发挥关键作用，解决了tmRNA·SmpB如何识别被截断的mRNA上的核糖体。
tmRNA is a bacterial small RNA having a structure resembling the upper half of tRNA and its 3′ end accepts alanine followed by binding to EF-Tu like tRNA. Instead of lacking a lower half of the cloverleaf structure including the anticodon, tmRNA has a short coding sequence for tag-peptide that serves as a target of cellular proteases. An elaborate coordination of two functions as tRNA and mRNA facilitates an irregular translation termed trans-translation: a single polypeptide is synthesized from two mRNA molecules. It allows resumption of translation stalled on a truncated mRNA, producing a chimeric polypeptide comprising the C-terminally truncated polypeptide derived from truncated mRNA and the C-terminal tag-peptide encoded by tmRNA. Trans-translation promotes recycling of the stalled ribosomes in the cell, and the resulting C-terminally tagged polypeptide is preferentially degraded by cellular proteases. Biochemical studies using in vitro trans-translation systems together with structural studies have unveiled the molecular mechanism of trans-translation, during which the upper and lower halves of tRNA are mimicked by the tRNA-like structure of tmRNA and a tmRNA-specific binding protein called SmpB, respectively. They mimic not only the tRNA structure but also its behavior perhaps at every step of the trans-translation process in the ribosome. Furthermore, the C-terminal tail of SmpB, which is unstructured in solution, occupies the mRNA path in the ribosome to play a crucial role in trans-translation, addressing how tmRNA·SmpB recognizes the ribosome stalled on a truncated mRNA.
登录
查看更多内容
影响因子：
3
作者：
Cheng, Kimberley;Ivanova, Natalia;Lindahl, Martin
通讯作者：
Lindahl, Martin
DOI：
10.1073/pnas.012602299
发表时间：
2002-01-22
影响因子：
11.1
作者：
Akerley, BJ;Rubin, EJ;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
3.6
作者：
Abe, Teppei;Sakaki, Kazutaka;Muto, Akira
通讯作者：
Muto, Akira
影响因子：
11.4
作者：
Felden, B;Hanawa, K;Crain, PF
通讯作者：
Crain, PF
影响因子：
2.1
作者：
Fujihara, A;Tomatsu, H;Muto, A
通讯作者：
Muto, A