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

Kejiou N. S. et al.

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.

D-Plex RNA-seq kit
D-Plex small RNA-seq

Share this article

May, 2023


Products used in this publication

  • Small RNA library preparation with UMI for Illumina
    D-Plex Small RNA-seq Library Prep Kit x24
  • D-Plex Total RNA-seq Kit for Illumina
    D-Plex Total RNA-seq Kit for Illumina


  • FASEB Biological Methylation: Fundamental Mechanisms
    Porto, Portugal
    Jul 28-Aug 1, 2024


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy