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Record W4301394819 · doi:10.1101/2022.10.03.510264

AKIR-1 Regulates Proteasome Localization and Function in <i>Caenorhabditis elegans</i>

2022· preprint· en· W4301394819 on OpenAlexfundno aff
Johanna Pispa, Elisa Mikkonen, Leena Arpalahti, Congyu Jin, Carmen Martínez-Fernández, Julián Cerón, Carina I. Holmberg

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics, Aging, and Longevity in Model Organisms
Canadian institutionsnot available
FundersNational Institutes of HealthUniversity of British ColumbiaSigrid Juséliuksen SäätiöSuomen KulttuurirahastoAgencia Estatal de InvestigaciónHelsingin YliopistoMinisterio de Ciencia, Innovación y UniversidadesAcademy of FinlandMedicinska Understödsföreningen Liv och Hälsa
KeywordsProteasomeCaenorhabditis elegansCell biologyBiologyProteostasisUbiquitinSubcellular localizationRNA interferenceNuclear localization sequenceCytoplasmProtein degradationMulticellular organismF-box proteinGeneUbiquitin ligaseBiochemistryRNA

Abstract

fetched live from OpenAlex

Abstract Regulated protein clearance is vital for cells to maintain protein homeostasis and the conditions essential for survival. The primary machinery for intracellular protein degradation is the ubiquitin– proteasome system (UPS), by which ubiquitin-tagged proteins are degraded by the proteasome. Proteasomes are present both in the cytoplasm and the nucleus, but the mechanisms coordinating proteasome activity and its subcellular localization in a multicellular organism are still unclear. Here, we identified the nuclear protein-encoding gene akir-1 as a proteasome regulator in a genome-wide Caenorhabditis elegans ( C. elegans ) RNAi screen. We show that the depletion of akir-1 causes accumulation of endogenous polyubiquitinated proteins in the nuclei of intestinal cells, concomitant with slower in vivo proteasomal degradation in this subcellular compartment. Remarkably, the loss of akir-1 does not induce an accumulation of polyubiquitinated proteins in oocyte nuclei, though akir-1 is essential for the nuclear localization of proteasomes in both cell types. We further show that the importin family member ima-3 genetically interacts with akir-1 , and affects subcellular distribution of polyubiquitinated proteins in intestinal cells. We show for the first time that conserved AKIR-1 is important for the nuclear transport of proteasomes in a multicellular organism, suggesting a role for AKIR-1 in the maintenance of proteostasis.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.193
Teacher spread0.186 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenetics, Aging, and Longevity in Model Organisms→French-language works237,207→