9HVQ

Structure of the transcribing Pol II-DSIF-PAF-SPT6-RECQL5 complex

Summary for 9HVQ

• Entry DOI: 10.2210/pdb9hvq/pdb
• EMDB information: 52440 52443
• Descriptor: DNA-directed RNA polymerase subunit, DNA-directed RNA polymerases I, II, and III subunit RPABC5, DNA-directed RNA polymerase II subunit RPB11-a, ... (26 entities in total)
• Functional Keywords: transcription elongation, dna helicase, transcription-coupled repair, rna polymerase ii, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 24
• Total formula weight: 1363289.42

Authors

Zhang, L.,Zhang, S. (deposition date: 2024-12-31, release date: 2025-07-16)

Primary citation

Zhang, L.,Gordiyenko, Y.,Morgan, T.,Franco, C.,Tufegdzic Vidakovic, A.,Zhang, S.
Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Abnormally fast transcription elongation can lead to detrimental consequences such as transcription-replication collisions, altered alternative splicing patterns and genome instability. Therefore, elongating RNA polymerase II (Pol II) requires mechanisms to slow its progression, yet the molecular basis of transcription braking remains unclear. RECQL5 is a DNA helicase that functions as a general elongation factor by slowing down Pol II. Here we report cryo-electron microscopy structures of human RECQL5 bound to multiple transcription elongation complexes. Combined with biochemical analysis, we identify an α-helix of RECQL5 responsible for binding Pol II and slowdown of transcription elongation. We further reveal that the transcription-coupled DNA repair (TCR) complex allows Pol II to overcome RECQL5-induced transcription braking through concerted actions of its translocase activity and competition with RECQL5 for engaging Pol II. Additionally, RECQL5 inhibits TCR-mediated Pol II ubiquitination to prevent activation of the DNA repair pathway. Our results suggest a model in which RECQL5 and the TCR complex coordinately regulate transcription elongation rates to ensure transcription efficiency while maintaining genome stability.

PubMed: 40624163
DOI: 10.1038/s41594-025-01586-6

Experimental method

ELECTRON MICROSCOPY (2 Å)