Base by Base24 Nov 2025

208: ZAK, Collided Ribosomes, and the Stress Switch

ZAK, Collided Ribosomes, and the Stress Switch

Music:
Enjoy the music based on this article at the end of the episode.

DOI:
10.1038/s41586-025-09772-8

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/zak-collided-ribosomes-and-the-stress-switch

️ Episode:
208: ZAK, Collided Ribosomes, and the Stress Switch

️ Season:
1

Article title:
ZAK activation at the collided ribosome

Journal:
Nature

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-11-24.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited sections covering ZAK constitutive ribosome binding, collision sensing via RACK1, RIH and RIM motifs, SAM-domain dimerization as activation switch, SERBP1 regulation, CLIP-seq mapping to ES7/ES6b/c, and downstream MAPK signaling.
- transcript topics: RSR overview and ZAK as central kinase; Constitutive ribosome binding of ZAK to the 40S via pin and ES7-patch; Collision interface: RACK1, RIH, and RIM motifs; SAM-domain dimerization as activation switch; SERBP1 competition at FPxL motif on RACK1; CLIP-seq mapping ES7 and ES6b/c on 18S rRNA

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- ZAK activation is triggered by ribosome collisions via SAM-domain dimerization at the collision interface.
- RACK1 acts as the collision scaffold bridging ZAK to both collided ribosomes, with ZAK interacting through RIH and RIM motifs.
- RIH anchors ZAK to RACK1 and is necessary for binding and activation.
- FPxL motif (RIM) is strictly required for ZAK activation on collided ribosomes, but not for initial binding.
- SERBP1 competes for the RACK1 FPxL binding site and acts as a negative regulator of ZAK activation.
- ZAK pin (eS27-pin) anchors ZAK to the 40S subunit via W768; ES7-patch also contributes to ribosome binding.

QC result: Pass.

Chapters

(00:00:00) - The cell's ribotoxic stress response
(00:05:10) - The Rack 1 Collapse Sensor
(00:09:55) - How does the ZK SAM domains dimerize to trigger cell
(00:12:16) - When We Collide

Det här avsnittet är hämtat från ett öppet RSS-flöde och publiceras inte av Podme. Det kan innehålla reklam.

Avsnitt(445)

444: Many-eyes or Sentinels? How Cost Curvature Shapes Collective Vigilance

Pilgrim C et al., PNAS - A minimal analytical model shows that whether animal groups adopt distributed low-level vigilance (many-eyes) or concentrated high-vigilance roles (sentinels) depends on how i...

19 Aug 24min

443: 5D‑ASO boosts exon 51 skipping and restores dystrophin in DMD models

Feng P et al., PNAS - This paper describes a bipartite antisense oligonucleotide (5D‑ASO) design that appends a short 5′ splice site decoy tail to improve exon skipping, demonstrating robust efficacy ...

18 Aug 19min

442: When pumps go missing: Ca2+ control of PMCA2 in Tmc1 deafness mutants

Rolseth AB et al., Proceedings of the National Academy of Sciences (PNAS) - This study links reduced Ca2+ entry through mutant TMC1 mechanotransducer channels to decreased PMCA2 pump density in outer ...

17 Aug 22min

441: Evolutionary mapping of Cav1.3 functional sites

Tang X et al., PNAS - The authors apply an evolutionary sequence-covariation model to the Cav1.3 (CACNA1D) α1-subunit, map predicted pathogenicity onto structural models, and validate five predicted s...

14 Aug 24min

440: DENV-4: Suppressing DNA Repair and Causing Genome Damage

Lamkina EN et al., PNAS - This episode reviews a PNAS brief report showing that DENV-4 infection induces marked DNA damage in infected cells while broadly suppressing transcription of DNA repair pathw...

12 Aug 23min

439: Coembedding Sequence and Structure: CLSS Maps the Protein Universe

Longo LM et al., PNAS - This episode summarizes a PNAS study introducing CLSS, a contrastive two-tower protein language model that coembeds domain sequences, structures, and subsequences into a shared...

11 Aug 23min

438: Mapping AIRE: a proactive atlas of 9,790 missense variants

Axakova A et al., The American Journal of Human Genetics - Axakova et al. generated a variant effect map for AIRE using an insulin‑promoter GFP reporter in HEK293 cells to measure the functional impac...

10 Aug 24min

437: Cell villages and Dirichlet modeling map human cell fitness genetics

Hanson C et al., The American Journal of Human Genetics - Hanson et al. combine pooled multi-donor human neural progenitor cell "villages" with Townlet, a hierarchical Dirichlet regression model, to e...

9 Aug 28min