Evidence map›Paper›PMID 37224531›Full record

ArticleNucleic acids research2023

Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling.

Nevraj S Kejiou, Lena Ilan, Stefan Aigner, Enching Luo, Tori Tonn, Hakan Ozadam, Muyoung Lee, Gregory B Cole, Ines Rabano, Nishani Rajakulendran and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

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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

17 authors at 4 institutions in 2 countries.

Nevraj S KejiouDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada.
Lena IlanDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada.
Stefan AignerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Enching LuoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Tori TonnDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Hakan OzadamDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Muyoung LeeDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Gregory B ColeDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada.
Ines RabanoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Nishani RajakulendranLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Brian A YeeDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Hamed S NajafabadiDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Trevor F MoraesDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-9883-6145
Stephane AngersDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Can CenikDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Alexander F PalazzoDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-9700-1995
University of Toronto · CAUniversity of California San Diego · USThe University of Texas at Austin · USMcGill University and Génome Québec Innovation Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In light of the numerous studies identifying post-transcriptional regulators on the surface of the endoplasmic reticulum (ER), we asked whether there are factors that regulate compartment specific mRNA translation in human cells. Using a proteomic survey of spatially regulated polysome interacting proteins, we identified the glycolytic enzyme Pyruvate Kinase M (PKM) as a cytosolic (i.e. ER-excluded) polysome interactor and investigated how it influences mRNA translation. We discovered that the PKM-polysome interaction is directly regulated by ADP levels-providing a link between carbohydrate metabolism and mRNA translation. By performing enhanced crosslinking immunoprecipitation-sequencing (eCLIP-seq), we found that PKM crosslinks to mRNA sequences that are immediately downstream of regions that encode lysine- and glutamate-enriched tracts. Using ribosome footprint protection sequencing, we found that PKM binding to ribosomes causes translational stalling near lysine and glutamate encoding sequences. Lastly, we observed that PKM recruitment to polysomes is dependent on poly-ADP ribosylation activity (PARylation)-and may depend on co-translational PARylation of lysine and glutamate residues of nascent polypeptide chains. Overall, our study uncovers a novel role for PKM in post-transcriptional gene regulation, linking cellular metabolism and mRNA translation.

Indexed as

Poly ADP RibosylationProtein BiosynthesisPyruvate KinaseGlutamatesHumansLysineProteomicsRibosomesGlutamatesLysinePyruvate Kinase

Identifiers

PMID37224531
PMCPMC10325899
OpenAlexW4378070266

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.