SNAP output for PDB entry 7slp [SNAP web server]

PDB-id

7slp; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein-RNA

Method

cryo-EM (4.1 Å)

Summary

cryo-EM structure of 7sk core rnp with linear RNA

Reference

Yang Y, Liu S, Egloff S, Eichhorn CD, Hadjian T, Zhen J, Kiss T, Zhou ZH, Feigon J (2022): "Structural basis of RNA conformational switching in the transcriptional regulator 7SK RNP." Mol.Cell, 82, 1724. doi: 10.1016/j.molcel.2022.03.001.

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.