Advance description
The metabolic enzyme PKM2 accumulates in the nucleus in various cancer cells. In this study, researchers found that PKM2 binds to structures called G-quadruplexes (rG4) forming on precursor mRNAs. The balance of folded and unfolded rG4s controls the transcriptional output of rG4-containing RNAs (rG4ome). The rG4ome encodes components related to epithelial-to-mesenchymal transition (e.g., a process that allows tumors to grow and spread) and higher rG4 levels, which are associated with poorer patient survival outcomes in different cancer types. Further, removing PKM2 from the nucleus reduces tumor growth and metastasis.
What is exciting about this article?
A "regulon" is a set of genes that are controlled by a single regulatory protein. This study identifies G-quadruplex structures as gene regulatory elements that are jointly regulated by an RNA binding protein. RNAs predominantly containing RNA G-quadruplexes are part of a pro-proliferative program associated with tumor growth and metastasis, targeting nuclear RNA binding proteins that stabilize G-quadruplexes might be of therapeutic value to combat metastatic disease.
Grant support
- ZIA AR041201 (Hafner, Markus) Dissecting the Role of Shuttling mRNA Binding Proteins in Nucleocytoplasmic RNA Transport.
- ZIA AR041205 (Hafner, Markus) Integration of the Results from Systems-Level Determination of Cis-Acting Elements into High-Resolution Maps of Posttranscriptional Regulatory Events.
Research Areas:
Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.