Polycomb repressive complex 2 binds RNA irrespective of stereochemistry Academic Article uri icon

abstract

  • The Polycomb Repressive Complex 2 (PRC2) interacts promiscuously with G-quadruplex (G4) RNA structures. Herein, we tested the limit of this promiscuity by exploring the interaction of PRC2 with G4 RNAs comprised of l-ribonucleic acids (l-RNA), the enantiomer of naturally occurring d-RNA. Remarkably, we find that PRC2 binds similarly to both d- and l-G4 RNAs, suggesting that these interactions are independent of stereochemistry. Moreover, we show that d- and l-RNAs bind to the same site on PRC2, enabling l-G4 RNAs to outcompete native substrates for binding. This work challenges the prevailing assumption that l-oligonucleotides are "invisible" to native biology and provides a unique opportunity to develop a novel class of PRC2 inhibitors based on nuclease-resistant l-RNA.

altmetric score

  • 1

author list (cited authors)

  • Deckard, C. E., & Sczepanski, J. T.

citation count

  • 2

publication date

  • October 2018