ArticleACS chemical biology2016
An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Structural and computational studies of HIV-1 RNA.RNA biology · 2024Review
- A Novel Time-Resolved Fluorescence Resonance Energy Transfer Assay for the Discovery of Small-Molecule Inhibitors of HIV-1 Tat-Regulated Transcription.International journal of molecular sciences · 2023Article
- Building Blocks of Artificial CRISPR-Based Systems beyond Nucleases.International journal of molecular sciences · 2022Review
- Methods for the directed evolution of biomolecular interactions.Trends in biochemical sciences · 2022Review
- Directed evolution of orthogonal RNA-RBP pairs through library-vs-library in vitro selection.Nucleic acids research · 2022Article
- RNA-Binding Macrocyclic Peptides.Frontiers in molecular biosciences · 2022Review
- Conformational dynamics and energetics of viral RNA recognition by lab-evolved proteins.Physical chemistry chemical physics : PCCP · 2021Article
- Affinity and Structural Analysis of the U1A RNA Recognition Motif with Engineered Methionines to Improve Experimental Phasing.Crystals · 2021Article
- Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors.The Journal of biological chemistry · 2020Article
- Review
- The potential of engineered eukaryotic RNA-binding proteins as molecular tools and therapeutics.Wiley interdisciplinary reviews. RNA · 2020Review
- Article
- Face-time with TAR: Portraits of an HIV-1 RNA with diverse modes of effector recognition relevant for drug discovery.The Journal of biological chemistry · 2019Review
- Exosomal packaging of trans-activation response element (TAR) RNA by HIV-1 infected cells: a pro-malignancy message delivery to cancer cells.Molecular biology reports · 2019Review
- Molecular recognition of a branched peptide with HIV-1 Rev Response Element (RRE) RNA.Bioorganic & medicinal chemistry · 2019Article
- Structure of HIV TAR in complex with a Lab-Evolved RRM provides insight into duplex RNA recognition and synthesis of a constrained peptide that impairs transcription.Nucleic acids research · 2018Article
- Amiloride as a new RNA-binding scaffold with activity against HIV-1 TAR.MedChemComm · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Potent and selective recognition and modulation of disease-relevant RNAs remain a daunting challenge. We previously examined the utility of the U1A N-terminal RNA recognition motif as a scaffold for tailoring new RNA hairpin recognition and showed that as few as one or two mutations can result in moderate affinity (low μM dissociation constant) for the human immunodeficiency virus (HIV) trans-activation response element (TAR) RNA, an RNA hairpin controlling transcription of the human immunodeficiency virus (HIV) genome. Here, we use yeast display and saturation mutagenesis of established RNA-binding regions in U1A to identify new synthetic proteins that potently and selectively bind TAR RNA. Our best candidate has truly altered, not simply broadened, RNA-binding selectivity; it binds TAR with subnanomolar affinity (apparent dissociation constant of ∼0.5 nM) but does not appreciably bind the original U1A RNA target (U1hpII). It specifically recognizes the TAR RNA hairpin in the context of the HIV-1 5'-untranslated region, inhibits the interaction between TAR RNA and an HIV trans-activator of transcription (Tat)-derived peptide, and suppresses Tat/TAR-dependent transcription. Proteins described in this work are among the tightest TAR RNA-binding reagents-small molecule, nucleic acid, or protein-reported to date and thus have potential utility as therapeutics and basic research tools. Moreover, our findings demonstrate how a naturally occurring RNA recognition motif can be dramatically resurfaced through mutation, leading to potent and selective recognition-and modulation-of disease-relevant RNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.