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TitleStructural basis of RNA conformational switching in the transcriptional regulator 7SK RNP.
Journal, issue, pagesMol Cell, Vol. 82, Issue 9, Page 1724-11736.e7, Year 2022
Publish dateMay 5, 2022
AuthorsYuan Yang / Shiheng Liu / Sylvain Egloff / Catherine D Eichhorn / Tanya Hadjian / James Zhen / Tamás Kiss / Z Hong Zhou / Juli Feigon /
PubMed Abstract7SK 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 ...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.
External linksMol Cell / PubMed:35320752 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 4.1 Å
Structure data

25197

7slp

EMDB-25197, PDB-7slp:
Cryo-EM structure of 7SK core RNP with linear RNA
Method: EM (single particle) / Resolution: 4.1 Å

25198

7slq

EMDB-25198, PDB-7slq:
Cryo-EM structure of 7SK core RNP with circular RNA
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN/RNA / non-coding RNA / La-related protein / methylphosphate capping enzyme / transcription regulation / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex

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