RNA conformational propensities determine cellular activity.
Nature
; 617(7962): 835-841, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-37198487
ABSTRACT
Cellular processes are the product of interactions between biomolecules, which associate to form biologically active complexes1. These interactions are mediated by intermolecular contacts, which if disrupted, lead to alterations in cell physiology. Nevertheless, the formation of intermolecular contacts nearly universally requires changes in the conformations of the interacting biomolecules. As a result, binding affinity and cellular activity crucially depend both on the strength of the contacts and on the inherent propensities to form binding-competent conformational states2,3. Thus, conformational penalties are ubiquitous in biology and must be known in order to quantitatively model binding energetics for protein and nucleic acid interactions4,5. However, conceptual and technological limitations have hindered our ability to dissect and quantitatively measure how conformational propensities affect cellular activity. Here we systematically altered and determined the propensities for forming the protein-bound conformation of HIV-1 TAR RNA. These propensities quantitatively predicted the binding affinities of TAR to the RNA-binding region of the Tat protein and predicted the extent of HIV-1 Tat-dependent transactivation in cells. Our results establish the role of ensemble-based conformational propensities in cellular activity and reveal an example of a cellular process driven by an exceptionally rare and short-lived RNA conformational state.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Viral
/
Activación Transcripcional
/
Duplicado del Terminal Largo de VIH
/
VIH-1
/
Productos del Gen tat del Virus de la Inmunodeficiencia Humana
/
Conformación de Ácido Nucleico
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nature
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos