代谢酶 PKM2 的核定位在各种癌症类型中广泛观察到。我们将核 PKM2 确定为一种非典型 RNA 结合蛋白 (RBP)，它与前体 mRNA (pre-mRNA) 中的折叠 RNA G 四链体 (rG4) 结构特异性相互作用。 PKM2 在 rG4 上的占据可防止抑制性 RBP（例如 HNRNPF）的结合，并促进含有 rG4 的前 mRNA（“rG4ome”）的表达。我们观察到 rG4ome 在上皮间质转化过程中上调，并且 rG4 丰度与不同癌症类型的患者生存率呈负相关。通过阻止 PKM2 的核积累，我们可以抑制三阴性乳腺癌细胞中的 rG4ome，并减少体外和异种移植小鼠模型中癌细胞的迁移和侵袭。我们的数据表明，RBP 控制的折叠和未折叠 rG4 的平衡会影响肿瘤进展过程中的基因表达。由 Elsevier Inc. 出版。

Nuclear localization of the metabolic enzyme PKM2 is widely observed in various cancer types. We identify nuclear PKM2 as a non-canonical RNA-binding protein (RBP) that specifically interacts with folded RNA G-quadruplex (rG4) structures in precursor mRNAs (pre-mRNAs). PKM2 occupancy at rG4s prevents the binding of repressive RBPs, such as HNRNPF, and promotes the expression of rG4-containing pre-mRNAs (the "rG4ome"). We observe an upregulation of the rG4ome during epithelial-to-mesenchymal transition and a negative correlation of rG4 abundance with patient survival in different cancer types. By preventing the nuclear accumulation of PKM2, we could repress the rG4ome in triple-negative breast cancer cells and reduce migration and invasion of cancer cells in vitro and in xenograft mouse models. Our data suggest that the balance of folded and unfolded rG4s controlled by RBPs impacts gene expression during tumor progression.Published by Elsevier Inc.