8P4D

Structural insights into human co-transcriptional capping - structure 4

8P4D の概要

• エントリーDOI: 10.2210/pdb8p4d/pdb
• EMDBエントリー: 17406
• 分子名称: DNA (32-MER), DNA-directed RNA polymerases I, II, and III subunit RPABC5, DNA-directed RNA polymerase II subunit RPB11-a, ... (19 entities in total)
• 機能のキーワード: rna polymerase ii, capping, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 749096.62

構造登録者

Garg, G.,Dienemann, C.,Farnung, L.,Schwarz, J.,Linden, A.,Urlaub, H.,Cramer, P. (登録日: 2023-05-20, 公開日: 2023-08-16)

主引用文献

Garg, G.,Dienemann, C.,Farnung, L.,Schwarz, J.,Linden, A.,Urlaub, H.,Cramer, P.
Structural insights into human co-transcriptional capping.
Mol.Cell, 83:2464-2477.e5, 2023

PubMed Abstract: Co-transcriptional capping of the nascent pre-mRNA 5' end prevents degradation of RNA polymerase (Pol) II transcripts and suppresses the innate immune response. Here, we provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryoelectron microscopy (cryo-EM) structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end. Addition of a GMP moiety can occur when the RNA is ∼22 nt long, sufficient to reach the active site of the guanylyltransferase. For subsequent cap(1) methylation, the methyltransferase CMTR1 binds the Pol II stalk and can receive RNA after it is grown to ∼29 nt in length. The observed rearrangements of capping factors on the Pol II surface may be triggered by the completion of catalytic reaction steps and are accommodated by domain movements in the elongation factor DRB sensitivity-inducing factor (DSIF).

PubMed: 37369200
DOI: 10.1016/j.molcel.2023.06.002

実験手法

ELECTRON MICROSCOPY (3.6 Å)