The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway
Summary: Ribosome collision because of translational stalling is recognized as a problematic event in translation by the E3 ubiquitin ligase Hel2, leading to non-canonical subunit dissociation followed by targeting of the faulty nascent peptides for degradation. Although Hel2-mediated quality contro...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721001911 |
| _version_ | 1818620652855230464 |
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| author | Yoshitaka Matsuo Toshifumi Inada |
| author_facet | Yoshitaka Matsuo Toshifumi Inada |
| author_sort | Yoshitaka Matsuo |
| collection | DOAJ |
| description | Summary: Ribosome collision because of translational stalling is recognized as a problematic event in translation by the E3 ubiquitin ligase Hel2, leading to non-canonical subunit dissociation followed by targeting of the faulty nascent peptides for degradation. Although Hel2-mediated quality control greatly contributes to maintenance of cellular protein homeostasis, its physiological role in dealing with endogenous substrates remains unclear. This study utilizes genome-wide analysis, based on selective ribosome profiling, to survey the endogenous substrates for Hel2. This survey reveals that Hel2 binds preferentially to the pre-engaged secretory ribosome-nascent chain complexes (RNCs), which translate upstream of targeting signals. Notably, Hel2 recruitment into secretory RNCs is elevated under signal recognition particle (SRP)-deficient conditions. Moreover, the mitochondrial defects caused by insufficient SRP are enhanced by hel2 deletion, along with mistargeting of secretory proteins into mitochondria. These findings provide insights into risk management in the secretory pathway that maintains cellular protein homeostasis. |
| first_indexed | 2024-12-16T17:56:47Z |
| format | Article |
| id | doaj.art-12e36acbbfbf4fbb8ed823f4b352bfbe |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-16T17:56:47Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-12e36acbbfbf4fbb8ed823f4b352bfbe2022-12-21T22:22:09ZengElsevierCell Reports2211-12472021-03-013412108877The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathwayYoshitaka Matsuo0Toshifumi Inada1Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Corresponding authorGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Division of RNA and Gene Regulation, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Corresponding authorSummary: Ribosome collision because of translational stalling is recognized as a problematic event in translation by the E3 ubiquitin ligase Hel2, leading to non-canonical subunit dissociation followed by targeting of the faulty nascent peptides for degradation. Although Hel2-mediated quality control greatly contributes to maintenance of cellular protein homeostasis, its physiological role in dealing with endogenous substrates remains unclear. This study utilizes genome-wide analysis, based on selective ribosome profiling, to survey the endogenous substrates for Hel2. This survey reveals that Hel2 binds preferentially to the pre-engaged secretory ribosome-nascent chain complexes (RNCs), which translate upstream of targeting signals. Notably, Hel2 recruitment into secretory RNCs is elevated under signal recognition particle (SRP)-deficient conditions. Moreover, the mitochondrial defects caused by insufficient SRP are enhanced by hel2 deletion, along with mistargeting of secretory proteins into mitochondria. These findings provide insights into risk management in the secretory pathway that maintains cellular protein homeostasis.http://www.sciencedirect.com/science/article/pii/S2211124721001911Hel2ribosome ubiquitinationribosome stallingribosome collisionquality controlSRP |
| spellingShingle | Yoshitaka Matsuo Toshifumi Inada The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway Cell Reports Hel2 ribosome ubiquitination ribosome stalling ribosome collision quality control SRP |
| title | The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway |
| title_full | The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway |
| title_fullStr | The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway |
| title_full_unstemmed | The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway |
| title_short | The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway |
| title_sort | ribosome collision sensor hel2 functions as preventive quality control in the secretory pathway |
| topic | Hel2 ribosome ubiquitination ribosome stalling ribosome collision quality control SRP |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721001911 |
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