Summary information and primary citation
- PDB-id
-
7slq;
DSSR-derived features in text and
JSON formats
- Class
- RNA binding protein-RNA
- Method
- cryo-EM (3.7 Å)
- Summary
- cryo-EM structure of 7sk core rnp with circular
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.
