Evidence map›Paper›PMID 25338081›Full record

ArticlePloS one2014

Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.

Ilona Patursky-Polischuk, Judith Kasir, Rachel Miloslavski, Zvi Hayouka, Mirit Hausner-Hanochi, Miri Stolovich-Rain, Pinchas Tsukerman, Moshe Biton, Rajini Mudhasani, Stephen N Jones and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5' TOP motifs.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  8. LARP1 on TOP of ribosome production.Wiley interdisciplinary reviews. RNA · 2018
    Review
  9. Review
  10. Trans-acting translational regulatory RNA binding proteins.Wiley interdisciplinary reviews. RNA · 2018
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. mTOR in health and in sickness.Journal of molecular medicine (Berlin, Germany) · 2015
    Review
  17. Article
  18. Review
  19. Review
  20. 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 at 1 institution in 1 country.

Ilona Patursky-PolischukDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Judith KasirDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Rachel MiloslavskiDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Zvi HayoukaDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Mirit Hausner-HanochiDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Miri Stolovich-RainDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Pinchas TsukermanLautenberg Center for General and Tumor Immunology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Moshe BitonLautenberg Center for General and Tumor Immunology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Rajini MudhasaniDepartment of Cell Biology, University of Massachusetts Medical School, North Worcester, Massachusetts, United States of America.
Stephen N JonesDepartment of Cell Biology, University of Massachusetts Medical School, North Worcester, Massachusetts, United States of America.
Oded MeyuhasDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
University of Massachusetts Chan Medical School · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation.

Indexed as

Protein BiosynthesisAmino AcidsAnimalsGene Expression RegulationHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceMice, KnockoutMicroRNAsMultiprotein ComplexesPhosphorylationRNA, MessengerSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinAmino AcidsMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MicroRNAsMultiprotein ComplexesRNA, MessengerTOR Serine-Threonine KinasesTSC1 protein, humanTsc1 protein, mouseTuberous Sclerosis Complex 1 ProteinTumor Suppressor Proteins

Identifiers

PMID25338081
PMCPMC4206288
OpenAlexW2049795209

What OpenQuestion holds

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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.