Evidence map›Paper›PMID 39231962›Full record

ArticleNature communications2024

The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation.

Agata N Makar, Alina Boraman, Peter Mosen, Joanne E Simpson, Jair Marques, Tim Michelberger, Stuart Aitken, Ann P Wheeler, Dominic Winter, Alex von Kriegsheim and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Cell entry mechanisms of porcine enteric coronaviruses.The Journal of biological chemistry · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Agata N MakarCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK.
Alina BoramanCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK.
Peter MosenInstitute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany.ORCID 0000-0001-5922-3805
Joanne E SimpsonCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK.
Jair MarquesCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK.
Tim MichelbergerCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK.
Stuart AitkenMRC Human Genetics Unit, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.ORCID 0000-0003-4867-4568
Ann P WheelerMRC Human Genetics Unit, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
Dominic WinterInstitute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany.ORCID 0000-0001-6788-6641
Alex von KriegsheimCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK.ORCID 0000-0002-4952-8573
Noor GammohCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, UK. noor.gammoh@ed.ac.uk.ORCID 0000-0001-9402-9581

Funding

Cancer Research UK (CRUK) C52370/A21586
6 · The paper itself

Abstract

Autophagy is a finely orchestrated process required for the lysosomal degradation of cytosolic components. The final degradation step is essential for clearing autophagic cargo and recycling macromolecules. Using a CRISPR/Cas9-based screen, we identify RNAseK, a highly conserved transmembrane protein, as a regulator of autophagosome degradation. Analyses of RNAseK knockout cells reveal that, while autophagosome maturation is intact, cargo degradation is severely disrupted. Importantly, lysosomal protease activity and acidification remain intact in the absence of RNAseK suggesting a specificity to autolysosome degradation. Analyses of lysosome fractions show reduced levels of a subset of hydrolases in the absence of RNAseK. Of these, the knockdown of PLD3 leads to a defect in autophagosome clearance. Furthermore, the lysosomal fraction of RNAseK-depleted cells exhibits an accumulation of the ESCRT-III complex component, VPS4a, which is required for the lysosomal targeting of PLD3. Altogether, here we identify a lysosomal hydrolase delivery pathway required for efficient autolysosome degradation.

Indexed as

AutophagosomesAutophagyEndosomal Sorting Complexes Required for TransportLysosomesCRISPR-Cas SystemsHEK293 CellsHeLa CellsHumansHydrolasesVacuolar Proton-Translocating ATPasesEndosomal Sorting Complexes Required for TransportHydrolasesVacuolar Proton-Translocating ATPases

Identifiers

PMID39231962
PMCPMC11374810

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.