Regulatory Mechanisms through RNA Conformational Switching and Dynamics

Bevilacqua, Philip C.; Tolbert, Blanton S.

doi:10.1016/j.jmb.2022.167794

Cited by 4 publications

(1 citation statement)

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“…Employing a combined chemical and enzymatic probing approach, the Bentley group demonstrated distinct RNA structural changes by a slow Pol II mutant, influencing widespread RNA processing ( 1 ). Recent findings in a variety of species have documented average speed of Pol II accelerates with age, contributing to the dysregulation of proteomes in aging adults ( 2 ). Such intricate RNA folding regulation by the speed of Pol II plays a central role in the adaptation, development and overall fitness of organisms ( 1–4 ).…”

Section: Discussionmentioning

confidence: 99%

Kinetic pathway of HIV-1 TAR cotranscriptional folding

Jin,

Zhang,

Song

et al. 2024

Nucleic Acids Research

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The Trans-Activator Receptor (TAR) RNA, located at the 5′-end untranslated region (5′ UTR) of the human immunodeficiency virus type 1 (HIV-1), is pivotal in the virus’s life cycle. As the initial functional domain, it folds during the transcription of viral mRNA. Although TAR’s role in recruiting the Tat protein for trans-activation is established, the detailed kinetic mechanisms at play during early transcription, especially at points of temporary transcriptional pausing, remain elusive. Moreover, the precise physical processes of transcriptional pause and subsequent escape are not fully elucidated. This study focuses on the folding kinetics of TAR and the biological implications by integrating computer simulations of RNA folding during transcription with nuclear magnetic resonance (NMR) spectroscopy data. The findings reveal insights into the folding mechanism of a non-native intermediate that triggers transcriptional pause, along with different folding pathways leading to transcriptional pause and readthrough. The profiling of the cotranscriptional folding pathway and identification of kinetic structural intermediates reveal a novel mechanism for viral transcriptional regulation, which could pave the way for new antiviral drug designs targeting kinetic cotranscriptional folding pathways in viral RNAs.

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Section: Discussionmentioning

confidence: 99%