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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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Length:
20 minutes
Released:
Dec 7, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.12.05.519155v1?rss=1
Authors: Wang, L., Xu, Y., Yun, S., Yuan, Q., Satpute-Krishnan, P., Ye, Y.
Abstract:
Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating a Translocation-Associated Quality Control (TAQC) mechanism that degrades clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. Here we use 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. Together, our data support a model that SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development.
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Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2022.12.05.519155v1?rss=1
Authors: Wang, L., Xu, Y., Yun, S., Yuan, Q., Satpute-Krishnan, P., Ye, Y.
Abstract:
Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating a Translocation-Associated Quality Control (TAQC) mechanism that degrades clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. Here we use 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. Together, our data support a model that SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Dec 7, 2022
Format:
Podcast episode
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