RNA conformational propensities determine cellular activity

Megan L. Ken, Rohit Roy, Ainan Geng, Laura R. Ganser, Akanksha Manghrani, Bryan R. Cullen, Ursula Schulze-Gahmen (), Daniel Herschlag () and Hashim M. Al-Hashimi ()
Additional contact information
Megan L. Ken: Duke University School of Medicine
Rohit Roy: Duke University School of Medicine
Ainan Geng: Duke University School of Medicine
Laura R. Ganser: Johns Hopkins University
Akanksha Manghrani: Duke University School of Medicine
Bryan R. Cullen: Duke University School of Medicine
Ursula Schulze-Gahmen: Gladstone Institute of Virology
Daniel Herschlag: Stanford University
Hashim M. Al-Hashimi: Columbia University

Nature, 2023, vol. 617, issue 7962, 835-841

Abstract: 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.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06080-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:617:y:2023:i:7962:d:10.1038_s41586-023-06080-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06080-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().