The cancer-promoting enzyme PKM2 binds RNA via a positively charged regulatory patch
- 1EMBL Heidelberg
Abstract
Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that coordinates energy production with biosynthetic demands in physiologically proliferating and cancer cells. PKM2 has also emerged as a non-canonical RNA-binding protein. Here, we combine targeted PKM2 mutagenesis with RNA-protein interaction assays, biochemical and biophysical analyses to define how RNA binding relates to PKM2 allosteric control and oligomeric state. We show that the allosteric activator fructose-1,6-bisphosphate (FBP) strongly reduces PKM2 binding to RNA. Mutants with impaired oligomerization show reduced RNA binding, and RNA association is favored by the tetrameric state. A positively charged surface patch in the FBP-binding region is essential for RNA binding and displays emergent properties. Single-residue variants further link RNA association to FBP-responsive tetrameric conformations. Our data integrate RNA binding with PKM2 allosteric regulation.
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BibTeX
@misc{sommerkamp2026cancerpromoting,
title = {{The cancer-promoting enzyme PKM2 binds RNA via a positively charged regulatory patch}},
author = {P. Sommerkamp and C. Schillinger and K. Lapouge and A. Biancolella and D. Ferring-Appel and M. W. Hentze},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753476},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753476v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The cancer-promoting enzyme PKM2 binds RNA via a positively charged regulatory patch
AU - P. Sommerkamp
AU - C. Schillinger
AU - K. Lapouge
AU - A. Biancolella
AU - D. Ferring-Appel
AU - M. W. Hentze
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.753476
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.753476v1
AB - Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that coordinates energy production with biosynthetic demands in physiologically proliferating and cancer cells. PKM2 has also emerged as a non-canonical RNA-binding protein. Here, we combine targeted PKM2 mutagenesis with RNA-protein interaction assays, biochemical and biophysical analyses to define how RNA binding relates to PKM2 allosteric control and oligomeric state. We show that the allosteric activator fructose-1,6-bisphosphate (FBP) strongly reduces PKM2 binding to RNA. Mutants with impaired oligomerization show reduced RNA binding, and RNA association is favored by the tetrameric state. A positively charged surface patch in the FBP-binding region is essential for RNA binding and displays emergent properties. Single-residue variants further link RNA association to FBP-responsive tetrameric conformations. Our data integrate RNA binding with PKM2 allosteric regulation.
ER -