9DCH
Single-stranded RNA-mediated PRC2 dimer
Summary for 9DCH
| Entry DOI | 10.2210/pdb9dch/pdb |
| EMDB information | 46722 46726 46751 |
| Descriptor | TERRAmut RNA, Isoform 2 of Histone-lysine N-methyltransferase EZH2, Polycomb protein SUZ12, ... (8 entities in total) |
| Functional Keywords | prc2, rna, rnp complex, chromatin modifier, gene regulation |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 13 |
| Total formula weight | 674675.85 |
| Authors | |
| Primary citation | Song, J.,Yao, L.,Gooding, A.R.,Thron, V.,Kasinath, V.,Cech, T.R. Diverse RNA Structures Induce PRC2 Dimerization and Inhibit Histone Methyltransferase Activity. Biorxiv, 2024 Cited by 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 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. PubMed: 39257770DOI: 10.1101/2024.08.29.610323 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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