Nuclear PKM2 binds pre-mRNA at folded G-quadruplexes and reveals their gene regulatory role

Nuclear translocation of the key metabolic enzyme Pyruvate Kinase Isoform 2 (PKM2) is widely observed in cancer, but its contribution to gene regulation and pathogenesis remains unclear. Here we find that PKM2 specifically recognized folded RNA G-quadruplex (rG4) structures in vitro with high affinity. In human cells, nuclear PKM2 bound thousands of precursor mRNAs at potential rG4 sites and translocation of PKM2 to the nucleus resulted in increased expression of rG4-containing mRNAs. PKM2 PARCLIP , RNA-Seq after nuclear PKM2 depletion or forced nuclear PKM2 expression