SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum.
SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum.
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DOI：
10.1016/j.celrep.2023.112028
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发表时间：
2023-01-31
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
翻译停滞导致的内质网 (ER) 易位子堵塞会触发核糖体 UFMylation，激活易位相关质量控制 (TAQC) 以降解堵塞的底物。细胞如何感知核糖体 UFMylation 来启动 TAQC 尚不清楚。我们进行了全基因组 CRISPR-Cas9 筛选，以鉴定一种名为 SAYSD1 的未表征膜蛋白，该蛋白有助于 TAQC。 SAYSD1 与 Sec61 易位子相关，并且还直接识别核糖体和 UFM1，与停滞的新生链接合以确保其通过 TRAPP 复合物运输到溶酶体进行降解。与 UFM1 缺陷一样，SAYSD1 缺失会导致易位停滞蛋白在 ER 处积累，并引发 ER 应激。重要的是，破坏果蝇中 UFM1 和 SAYSD1 依赖性 TAQC 会导致细胞内易位停滞的胶原蛋白积累、胶原蛋白沉积缺陷、基底膜异常和应激耐受性降低。因此，SAYSD1 充当 UFM1 传感器，与堵塞易位子部位的核糖体 UFMylation 协作，维护动物发育过程中的 ER 稳态。王等人。使用遗传筛选来确定 ER 中保护蛋白质易位的因素。他们将 SAYSD1 确定为 Sec61 相关调节因子，通过与 UFMylated 核糖体结合来感知易位子堵塞。 SAYSD1 促进易位停滞蛋白的清除，以维持 ER 蛋白稳态。
Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating translocation-associated quality control (TAQC) to degrade clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. We conduct a genome-wide CRISPR-Cas9 screen to identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. SAYSD1 associates with the Sec61 translocon and also recognizes both ribosome and UFM1 directly, engaging a stalled nascent chain to ensure its transport via the TRAPP complex to lysosomes for degradation. Like UFM1 deficiency, SAYSD1 depletion causes the accumulation of translocation-stalled proteins at the ER and triggers ER stress. Importantly, disrupting UFM1- and SAYSD1-dependent TAQC in Drosophila leads to intracellular accumulation of translocation-stalled collagens, defective collagen deposition, abnormal basement membranes, and reduced stress tolerance. Thus, SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development. Wang et al. use a genetic screen to identify factors safeguarding protein translocation at the ER. They establish SAYSD1 as a Sec61-associated regulator sensing translocon clogging by binding to UFMylated ribosomes. SAYSD1 facilitates the clearance of translocation-stalled proteins to maintain ER protein homeostasis.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1093/brain/awy135
发表时间：
2018-07-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Nahorski MS;Maddirevula S;Ishimura R;Alsahli S;Brady AF;Begemann A;Mizushima T;Guzmán-Vega FJ;Obata M;Ichimura Y;Alsaif HS;Anazi S;Ibrahim N;Abdulwahab F;Hashem M;Monies D;Abouelhoda M;Meyer BF;Alfadhel M;Eyaid W;Zweier M;Steindl K;Rauch A;Arold ST;Woods CG;Komatsu M;Alkuraya FS
通讯作者：
Alkuraya FS
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
影响因子：
9.8
作者：
Colin, Estelle;Daniel, Jens;Bonneau, Dominique
通讯作者：
Bonneau, Dominique
影响因子：
16
作者：
Huter, Paul;Arenz, Stefan;Wilson, Daniel N.
通讯作者：
Wilson, Daniel N.