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Lim, Chunghun
Neurogenetics & Ribonomics Laboratory (The Lim Lab)
Research Interests
  • Ribosome Biology, Translation, Neurodegeneration, Behavioral Genetics

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The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology

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Title
The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
Author
Park, JuminPark, JongminLee, JongbinLim, Chunghun
Issue Date
2021-09
Publisher
KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
Citation
BMB REPORTS, v.54, no.9, pp.439 - 450
Abstract
Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKa, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively deterrnine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities.
URI
https://scholarworks.unist.ac.kr/handle/201301/53989
URL
https://www.bmbreports.org/journal/view.html?doi=10.5483/BMBRep.2021.54.9.097
DOI
10.5483/BMBRep.2021.54.9.097
ISSN
1976-6696
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BIO_Journal Papers
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