7SLP

Cryo-EM structure of 7SK core RNP with linear RNA

Summary for 7SLP

• Entry DOI: 10.2210/pdb7slp/pdb
• EMDB information: 25197
• Descriptor: 7SK snRNA methylphosphate capping enzyme, La-related protein 7, Linear 7SK RNA, ... (4 entities in total)
• Functional Keywords: non-coding rna, la-related protein, methylphosphate capping enzyme, transcription regulation, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 116712.57

Authors

Yang, Y.,Liu, S.,Zhou, Z.H.,Feigon, J. (deposition date: 2021-10-24, release date: 2022-03-30, Last modification date: 2024-06-05)

Primary citation

Yang, Y.,Liu, S.,Egloff, S.,Eichhorn, C.D.,Hadjian, T.,Zhen, J.,Kiss, T.,Zhou, Z.H.,Feigon, J.
Structural basis of RNA conformational switching in the transcriptional regulator 7SK RNP.
Mol.Cell, 82:1724-, 2022

PubMed Abstract: 7SK non-coding RNA (7SK) negatively regulates RNA polymerase II (RNA Pol II) elongation by inhibiting positive transcription elongation factor b (P-TEFb), and its ribonucleoprotein complex (RNP) is hijacked by HIV-1 for viral transcription and replication. Methylphosphate capping enzyme (MePCE) and La-related protein 7 (Larp7) constitutively associate with 7SK to form a core RNP, while P-TEFb and other proteins dynamically assemble to form different complexes. Here, we present the cryo-EM structures of 7SK core RNP formed with two 7SK conformations, circular and linear, and uncover a common RNA-dependent MePCE-Larp7 complex. Together with NMR, biochemical, and cellular data, these structures reveal the mechanism of MePCE catalytic inactivation in the core RNP, unexpected interactions between Larp7 and RNA that facilitate a role as an RNP chaperone, and that MePCE-7SK-Larp7 core RNP serves as a scaffold for switching between different 7SK conformations essential for RNP assembly and regulation of P-TEFb sequestration and release.

PubMed: 35320752
DOI: 10.1016/j.molcel.2022.03.001

Experimental method

ELECTRON MICROSCOPY (4.1 Å)