RPL26/uL24 UFMylation is essential for ribosome-associated quality control at the endoplasmic reticulum.
RPL26/uL24 UFMylation is essential for ribosome-associated quality control at the endoplasmic reticulum.
复制标题
DOI：
10.1073/pnas.2220340120
复制
发表时间：
2023-04-18
影响因子：
11.1
通讯作者：
Kopito RR
中科院分区：
文献类型：
--
作者：
Scavone F;Gumbin SC;Da Rosa PA;Kopito RR
UFM 1是一种泛素样蛋白，其选择性地与结合到内质网（ER）的核糖体的大亚基（60 S）缀合，但这种修饰的具体生物学功能尚不清楚。在这里，我们表明，UFM化促进蛋白酶体介导的降解的逮捕多肽（AP），这是产生后分裂的核糖体，停止在共翻译易位的分泌蛋白到ER。我们认为，UFM化削弱了紧密密封的核糖体-转位子连接，从而允许胞质泛素-蛋白酶体和核糖体相关的质量控制机制访问ER-AP。在翻译胞质蛋白时停滞的核糖体被称为“停滞肽”（AP）的不完整新生链所破坏，这些新生链通过称为核糖体相关质量控制（RQC）途径的过程被泛素蛋白酶体系统（UPS）破坏。相比之下，核糖体上的AP在将分泌蛋白转运到内质网（ER-AP）时停滞，通过ER膜和紧密密封的核糖体-转运子连接（RTJ）与胞质溶胶屏蔽。这种连接是如何被破坏，使细胞溶质UPS机器和26 S蛋白酶体的访问易位和核糖体阻碍ER-AP是未知的。在这里，我们表明，UPS和RQC依赖的ER-AP降解严格要求泛素样（Ubl）蛋白UFM 1的60 S核糖体亚基在RTJ的共轭。因此，转座子结合的60 S亚基的UFM化调节RTJ以促进蛋白酶体和RQC机器接近ER-AP。
UFM1 is a ubiquitin-like protein that is selectively conjugated to the large (60S) subunit of ribosomes bound to the endoplasmic reticulum (ER), but the specific biological function of this modification is unclear. Here, we show that UFMylation facilitates proteasome-mediated degradation of arrest polypeptides (APs), which are generated following splitting of ribosomes that stall during cotranslational translocation of secretory proteins into the ER. We propose that UFMylation weakens the tightly sealed ribosome–translocon junction, thereby allowing the cytosolic ubiquitin–proteasome and ribosome-associated quality control machineries to access ER-APs. Ribosomes that stall while translating cytosolic proteins are incapacitated by incomplete nascent chains, termed “arrest peptides” (APs) that are destroyed by the ubiquitin proteasome system (UPS) via a process known as the ribosome-associated quality control (RQC) pathway. By contrast, APs on ribosomes that stall while translocating secretory proteins into the endoplasmic reticulum (ER-APs) are shielded from cytosol by the ER membrane and the tightly sealed ribosome–translocon junction (RTJ). How this junction is breached to enable access of cytosolic UPS machinery and 26S proteasomes to translocon- and ribosome-obstructing ER-APs is not known. Here, we show that UPS and RQC-dependent degradation of ER-APs strictly requires conjugation of the ubiquitin-like (Ubl) protein UFM1 to 60S ribosomal subunits at the RTJ. Therefore, UFMylation of translocon-bound 60S subunits modulates the RTJ to promote access of proteasomes and RQC machinery to ER-APs.
登录
查看更多内容
核糖体碰撞的全基因组调查。
影响因子：
8.8
作者：
Han P;Shichino Y;Schneider-Poetsch T;Mito M;Hashimoto S;Udagawa T;Kohno K;Yoshida M;Mishima Y;Inada T;Iwasaki S
通讯作者：
Iwasaki S
影响因子：
4.6
作者：
Arakawa S;Yunoki K;Izawa T;Tamura Y;Nishikawa S;Endo T
通讯作者：
Endo T
DOI：
10.1073/pnas.79.15.4540
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
ELDER, JH;ALEXANDER, S
通讯作者：
ALEXANDER, S
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：
16
作者：
Juszkiewicz, Szymon;Speldewinde, Shaun H.;Hegde, Ramanujan S.
通讯作者：
Hegde, Ramanujan S.