Dysregulation of ribosome-associated quality control elicits cognitive disorders via overaccumulation of TTC3

Significance Ribosome quality control (RQC) is a co-translational surveillance mechanism for degradation of nascent polypeptides in aberrantly stalled ribosomes during translation. Although dysfunction of RQC is suggested to elicit neurological disorders, molecular mechanisms therein have remained poorly understood. Here, we revealed that the loss of LTN1, an E3 ubiquitin ligase in the RQC pathway, significantly increases TTC3 and UFMylation signaling proteins in neurons. The abnormally accumulated TTC3 was stabilized by UFMylation signaling and prevented further accumulation of translationally arrested products by inhibiting translation initiation of selective genes. Instead, the aberrantly increased TTC3 protein caused dendritic and synaptic abnormalities associated with cognitive disorders. Thus, our data provide novel evidence of a possible molecular link between neuronal RQC dysfunction and cognitive disorders.

• Publication year

  2023

• Venue

  Proceedings of the National Academy of Sciences of the United States of America

• Publication date

  2023-03-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1073/pnas.2211522120PMID 36917672PMCID 10041068
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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