Summary information

PDB id
8fyh
Class
gene regulation
Method
cryo-EM (3.4 Å)
Summary
G4 RNA-mediated prc2 dimer
Reference
Song J, Gooding AR, Hemphill WO, Love BD, Robertson A, Yao L, Zon LI, North TE, Kasinath V, Cech TR (2023): "Structural basis for inactivation of PRC2 by G-quadruplex RNA." Science, 381, 1331-1337. doi: 10.1126/science.adh0059.
Abstract
Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RNA. In this work, we present a 3.3-Å-resolution cryo-electron microscopy structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2 by binding both protomers and inducing a protein interface composed of two copies of the catalytic subunit EZH2, thereby blocking nucleosome DNA interaction and histone H3 tail accessibility. Furthermore, an RNA-binding loop of EZH2 facilitates the handoff between RNA and DNA, another activity implicated in PRC2 regulation by RNA. We identified a gain-of-function mutation in this loop that activates PRC2 in zebrafish. Our results reveal mechanisms for RNA-mediated regulation of a chromatin-modifying enzyme.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, , parallel(4+0), UUUU

Base-block schematics in six views

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads

 1 glyco-bond=---- sugar=3.3. groove=---- planarity=0.494 type=other  nts=4 GGGG M.G1,M.G7,M.G13,M.G19
 2 glyco-bond=---- sugar=3333 groove=---- planarity=0.419 type=saddle nts=4 GGGG M.G2,M.G8,M.G14,M.G20
 3 glyco-bond=---- sugar=3333 groove=---- planarity=0.433 type=other  nts=4 GGGG M.G3,M.G9,M.G15,M.G21

List of 1 G4-helix

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 3 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=---- sugar=3.3. groove=---- WC-->Major nts=4 GGGG M.G1,M.G7,M.G13,M.G19
 2  glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G2,M.G8,M.G14,M.G20
 3  glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G3,M.G9,M.G15,M.G21
  step#1  pm(>>,forward)  area=19.83 rise=3.76 twist=23.3
  step#2  pm(>>,forward)  area=16.78 rise=3.46 twist=28.5
  strand#1 RNA glyco-bond=--- sugar=333 nts=3 GGG M.G1,M.G2,M.G3
  strand#2 RNA glyco-bond=--- sugar=.33 nts=3 GGG M.G7,M.G8,M.G9
  strand#3 RNA glyco-bond=--- sugar=333 nts=3 GGG M.G13,M.G14,M.G15
  strand#4 RNA glyco-bond=--- sugar=.33 nts=3 GGG M.G19,M.G20,M.G21

Download PDB file
Interactive view in 3Dmol.js

2 stacking diagrams
 1  glyco-bond=---- sugar=3.3. groove=---- WC-->Major nts=4 GGGG M.G1,M.G7,M.G13,M.G19
2 glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G2,M.G8,M.G14,M.G20
step#1 pm(>>,forward) area=19.83 rise=3.76 twist=23.3

Download PDB file
Interactive view in 3Dmol.js

 2  glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G2,M.G8,M.G14,M.G20
3 glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G3,M.G9,M.G15,M.G21
step#2 pm(>>,forward) area=16.78 rise=3.46 twist=28.5

Download PDB file
Interactive view in 3Dmol.js

List of 1 G4-stem

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 3 G-tetrad layers, 0 loops, INTRA-molecular, UUUU, parallel, descriptor, parallel(4+0)

 1  glyco-bond=---- sugar=3.3. groove=---- WC-->Major nts=4 GGGG M.G1,M.G7,M.G13,M.G19
 2  glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G2,M.G8,M.G14,M.G20
 3  glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG M.G3,M.G9,M.G15,M.G21
  step#1  pm(>>,forward)  area=19.83 rise=3.76 twist=23.3
  step#2  pm(>>,forward)  area=16.78 rise=3.46 twist=28.5
  strand#1  U RNA glyco-bond=--- sugar=333 nts=3 GGG M.G1,M.G2,M.G3
  strand#2  U RNA glyco-bond=--- sugar=.33 nts=3 GGG M.G7,M.G8,M.G9
  strand#3  U RNA glyco-bond=--- sugar=333 nts=3 GGG M.G13,M.G14,M.G15
  strand#4  U RNA glyco-bond=--- sugar=.33 nts=3 GGG M.G19,M.G20,M.G21

Download PDB file
Interactive view in 3Dmol.js