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Structural basis of RNA conformational switching in the transcriptional regulator 7SK RNP.
Yang, Yuan; Liu, Shiheng; Egloff, Sylvain; Eichhorn, Catherine D; Hadjian, Tanya; Zhen, James; Kiss, Tamás; Zhou, Z Hong; Feigon, Juli.
Afiliación
  • Yang Y; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Liu S; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Egloff S; Molecular, Cellular, and Developmental Biology Department (MCD), Centre de Biologie Intégrative (CBI), University of Toulouse, CNRS, UPS, 31062 Toulouse, France.
  • Eichhorn CD; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hadjian T; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zhen J; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kiss T; Molecular, Cellular, and Developmental Biology Department (MCD), Centre de Biologie Intégrative (CBI), University of Toulouse, CNRS, UPS, 31062 Toulouse, France; Biological Research Centre, Szeged, Temesvári krt. 62, 6726, Hungary.
  • Zhou ZH; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: hong.zhou@ucla.edu.
  • Feigon J; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: feigon@mbi.ucla.edu.
Mol Cell ; 82(9): 1724-1736.e7, 2022 05 05.
Article en En | MEDLINE | ID: mdl-35320752
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ARN / Factor B de Elongación Transcripcional Positiva Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ARN / Factor B de Elongación Transcripcional Positiva Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos