Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | Diverse RNA Structures Induce PRC2 Dimerization and Inhibit Histone Methyltransferase Activity. |
|---|---|
| Journal, issue, pages | bioRxiv, Year 2024 |
| Publish date | Aug 29, 2024 |
 Authors | Jiarui Song / Liqi Yao / Anne R Gooding / Valentin Thron / Vignesh Kasinath / Thomas R Cech |
| PubMed Abstract | Methyltransferase PRC2 (Polycomb Repressive Complex 2) introduces histone H3K27 trimethylation, a repressive chromatin mark, to tune the differential expression of genes. PRC2 is precisely regulated ...Methyltransferase PRC2 (Polycomb Repressive Complex 2) introduces histone H3K27 trimethylation, a repressive chromatin mark, to tune the differential expression of genes. PRC2 is precisely regulated by accessory proteins, histone post-translational modifications and, notably, RNA. Research on PRC2-associated RNA has mostly focused on the tight-binding G-quadruplex (G4) RNAs, which inhibit PRC2 enzymatic activity in vitro and in cells. Our recent cryo-EM structure provided a molecular mechanism for G4 RNA inactivating PRC2 via dimerization, but it remained unclear how diverse RNAs associate with and regulate PRC2. Here, we show that a single-stranded G-rich RNA and an atypical G4 structure called pUG-fold unexpectedly also mediate near-identical PRC2 dimerization resulting in inhibition of PRC2 methyltransferase activity. The conformational flexibility of arginine-rich loops within subunits EZH2 and AEBP2 of PRC2 can accommodate diverse RNA secondary structures, resulting in protein-RNA and protein-protein interfaces similar to those observed previously with G4 RNA. Furthermore, we address a recent report that failed to detect PRC2-associated RNAs in living cells by demonstrating the insensitivity of PRC2-RNA interaction to photochemical crosslinking. Our results support the significance of RNA-mediated PRC2 regulation by showing that this interaction is not limited to a single RNA secondary structure, consistent with the broad PRC2 transcriptome containing many G-tract RNAs incapable of folding into G4 structures. |
 External links | bioRxiv / PubMed:39257770 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.3 - 3.4 Å |
| Structure data |  EMDB-46722: Body 1 from multibody refinement of the single-stranded TERRAmut RNA-bound PRC2 dimer  EMDB-46726: Body 2 from multibody refinement of the single-stranded TERRAmut RNA-bound PRC2 dimer EMDB-46751, PDB-9dch: |
| Chemicals |  ChemComp-ZN: |
| Source |
|
 Keywords | GENE REGULATION / PRC2 / RNA / RNP complex / chromatin modifier |
homo sapiens (human)