9DCH

Single-stranded RNA-mediated PRC2 dimer

9DCH の概要

• エントリーDOI: 10.2210/pdb9dch/pdb
• EMDBエントリー: 46722 46726 46751
• 分子名称: TERRAmut RNA, Isoform 2 of Histone-lysine N-methyltransferase EZH2, Polycomb protein SUZ12, ... (8 entities in total)
• 機能のキーワード: prc2, rna, rnp complex, chromatin modifier, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 674675.85

構造登録者

Song, J.S.,Kasinath, V.K. (登録日: 2024-08-26, 公開日: 2025-03-12, 最終更新日: 2025-10-15)

主引用文献

Song, J.,Yao, L.,Gooding, A.R.,Thron, V.,Hemphill, W.O.,Goodrich, K.,Kasinath, V.,Cech, T.R.
RNA-induced PRC2 inhibition depends on the sequence of bound RNA.
Biorxiv, 2025

PubMed Abstract: Methyltransferase PRC2 (Polycomb Repressive Complex 2) deposits histone H3K27 trimethylation to establish and maintain epigenetic gene silencing. PRC2 is precisely regulated by accessory proteins, histone post-translational modifications and, particularly, 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, a mechanism explained by our recent cryo-EM structure showing G4 RNA-mediated PRC2 dimerization. However, PRC2 binds a wide variety of RNA sequences, and it remains unclear how diverse RNAs beyond G4 associate with and regulate PRC2. Here, we show that variations in RNA sequence elicit distinct effects on PRC2 function. A single-stranded G-rich RNA and an atypical G4 structure called a pUG-fold mediate PRC2 dimerization nearly identical to that induced by G4 RNA. In contrast, pyrimidine-rich RNAs, including a motif identified by CLIPseq in cells, do not induce PRC2 dimerization and instead bind PRC2 monomers with retention of methyltransferase activity. Only RNAs that dimerize PRC2 compete with nucleosome binding and inhibit PRC2 methyltransferase activity. CRISPR-dCas9 was adapted to localize different RNA elements onto a PRC2-targeted gene, revealing RNA sequence specificity for PRC2 regulation in cells. Thus, PRC2 binds many different RNAs with similar affinity, however, the functional effect on enzymatic activity depends entirely on the sequence of the bound RNA, a conclusion potentially applicable to any RNA- binding protein with a large transcriptome.

PubMed: 39257770
DOI: 10.1101/2024.08.29.610323

実験手法

ELECTRON MICROSCOPY (3.4 Å)