Defective Human SRP Induces Protein Quality Control and Triggers Stress Response.
Defective Human SRP Induces Protein Quality Control and Triggers Stress Response.
复制标题
缺陷人类SRP诱导蛋白质质量控制，并触发压力反应。
DOI：
10.1016/j.jmb.2022.167832
复制
发表时间：
2022-11-30
影响因子：
5.6
通讯作者：
Karamyshev, Andrey L.
中科院分区：
文献类型：
--
作者：
Tikhonova, Elena B.;Guarnizo, Sneider Alexander Gutierrez;Kellogg, Morgana K.;Karamyshev, Alexander;Dozmorov, Igor M.;Karamysheva, Zemfira N.;Karamyshev, Andrey L.
关键词：
异常蛋白产生的调节(RAPP)是哺乳动物细胞中的一种蛋白质质量控制。在核糖体合成过程中，RAPP降解不能与天然相互作用伙伴结合的新生蛋白质的mRNAs。然而，人们对该途径的分子机制、底物或其特异性知之甚少。信号识别颗粒(SRP)是分泌蛋白的第一个相互作用伙伴。当新生多肽从核糖体出口隧道暴露出来时，它识别它们的信号序列。在这里，我们通过耗尽人SRP54(SRP亚单位)在整个转录组水平上揭示了RAPP途径的共性。这种耗尽触发了RAPP，并导致编码一些分泌和膜蛋白的mRNAs表达减少。SRP54的缺失还导致HSP70/40/90伴侣(HSPA1A、DNAJB1、HSP90AA1等)的特定网络急剧上调，增加核糖体相关的泛素化，以及RPS27和RPS27L表达的变化，表明核糖体重排。这些结果证明了蛋白质运输、信使核糖核酸和蛋白质质量控制缺陷的复杂性，并提供了更好的了解它们在核糖体中的机制。
Regulation of Aberrant Protein Production (RAPP) is a protein quality control in mammalian cells. RAPP degrades mRNAs of nascent proteins not able to associate with their natural interacting partners during synthesis at the ribosome. However, little is known about the molecular mechanism of the pathway, its substrates, or its specificity. The Signal Recognition Particle (SRP) is the first interacting partner for secretory proteins. It recognizes signal sequences of the nascent polypeptides when they are exposed from the ribosomal exit tunnel. Here, we reveal the generality of the RAPP pathway on the whole transcriptome level through depletion of human SRP54, an SRP subunit. This depletion triggers RAPP and leads to decreased expression of the mRNAs encoding a number of secretory and membrane proteins. The loss of SRP54 also leads to the dramatic upregulation of a specific network of HSP70/40/90 chaperones (HSPA1A, DNAJB1, HSP90AA1, and others), increased ribosome associated ubiquitination, and change in expression of RPS27 and RPS27L suggesting ribosome rearrangement. These results demonstrate the complex nature of defects in protein trafficking, mRNA and protein quality control, and provide better understanding of their mechanisms at the ribosome.
登录
查看更多内容
影响因子：
16
作者：
D'Orazio KN;Green R
通讯作者：
Green R
影响因子：
8.8
作者：
Jomaa A;Eitzinger S;Zhu Z;Chandrasekar S;Kobayashi K;Shan SO;Ban N
通讯作者：
Ban N
影响因子：
5.6
作者：
Hsieh HH;Shan SO
通讯作者：
Shan SO
影响因子：
16.6
作者：
Garzia, Aitor;Jafarnejad, Seyed Mehdi;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
64.5
作者：
Hsieh, JC;Lee, L;Holdener, BC
通讯作者：
Holdener, BC