An equilibrium-dependent retroviral mRNA switch regulates translational recoding.
An equilibrium-dependent retroviral mRNA switch regulates translational recoding.
复制标题
DOI：
10.1038/nature10657
复制
发表时间：
2011-11-27
期刊：
影响因子：
64.8
通讯作者：
D'Souza, Victoria M.
中科院分区：
文献类型：
--
作者：
Houck-Loomis, Brian;Durney, Michael A.;Salguero, Carolina;Shankar, Neelaabh;Nagle, Julia M.;Goff, Stephen P.;D'Souza, Victoria M.
大多数逆转录病毒需要对病毒信使 RNA 终止密码子进行翻译重新编码，以在病毒组装过程中保持结构蛋白 (Gag) 和酶促蛋白 (Pol) 的精确比例。 Pol 通过核糖体移码或通读 gag 终止密码子专门表达为 Gag-Pol 融合。这两种机制很少发生，仅影响 5-10% 的翻译核糖体，从而使病毒能够维持关键的 Gag 与 Gag-Pol 比率。尽管人们知道重新编码事件的频率是由顺式RNA基序调节的，但目前还没有关于如何维持关键蛋白质比例的机制解释。在这里，我们展示了鼠白血病病毒重新编码信号的核磁共振结构，并表明质子化依赖性开关的发生诱导了活性构象。这种平衡使得在生理 pH 值下，活性、通读允许构象的分布约为 6%：该水平与体内蛋白质数量相关。 RNA 通过高度灵敏的化学机械耦合发挥作用，经过调整以确保最佳的通读频率。对移码信号的类似观察表明，这种新颖的基于平衡的机制可能在翻译重新编码中具有普遍作用。
Most retroviruses require translational recoding of a viral messenger RNA stop codon to maintain a precise ratio of structural (Gag) and enzymatic (Pol) proteins during virus assembly. Pol is expressed exclusively as a Gag–Pol fusion either by ribosomal frameshifting or by read-through of the gag stop codon. Both of these mechanisms occur infrequently and only affect 5–10% of translating ribosomes, allowing the virus to maintain the critical Gag to Gag–Pol ratio. Although it is understood that the frequency of the recoding event is regulated by cis RNA motifs, no mechanistic explanation is currently available for how the critical protein ratio is maintained. Here we present the NMR structure of the murine leukaemia virus recoding signal and show that a protonation-dependent switch occurs to induce the active conformation. The equilibrium is such that at physiological pH the active, read-through permissive conformation is populated at approximately 6%: a level that correlates with in vivo protein quantities. The RNA functions by a highly sensitive, chemo-mechanical coupling tuned to ensure an optimal read-through frequency. Similar observations for a frameshifting signal indicate that this novel equilibrium-based mechanism may have a general role in translational recoding.
登录
查看更多内容
影响因子：
6.1
作者：
Agirrezabala, Xabier;Frank, Joachim
通讯作者：
Frank, Joachim
影响因子：
64.5
作者：
PHILIPSON, L;ANDERSSON, P;GESTELAND, R
通讯作者：
GESTELAND, R
影响因子：
5
作者：
Giedroc, David P.;Cornish, Peter V.
通讯作者：
Cornish, Peter V.
影响因子：
64.8
作者：
Namy O;Moran SJ;Stuart DI;Gilbert RJ;Brierley I
通讯作者：
Brierley I
DOI：
10.1073/pnas.0506166102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Cornish, PV;Hennig, M;Giedroc, DP
通讯作者：
Giedroc, DP