RNA targeting through binding of small molecules: Studies on t-RNA binding by the cytotoxic protoberberine alkaloidcoralyne

2009 ◽  
Vol 5 (3) ◽  
pp. 244-254 ◽  
Author(s):  
Md. Maidul Islam ◽  
Prateek Pandya ◽  
Surat Kumar ◽  
Gopinatha Suresh Kumar
Keyword(s):  
Small Molecules ◽  
Rna Binding ◽  
Rna Targeting

scholarly journals Inhibition of SARS-CoV-2 by Targeting Conserved Viral RNA Structures and Sequences

2021 ◽  
Vol 9 ◽  
Author(s):  
Shalakha Hegde ◽  
Zhichao Tang ◽  
Junxing Zhao ◽  
Jingxin Wang
Keyword(s):  
Small Molecules ◽  
Rna Binding ◽  
Antiviral Drug ◽  
Viral Rna ◽  
Rna Structures ◽  
Drug Candidates ◽  
Novel Approach ◽  
Rna Targeting ◽  
New Type ◽  
Chimeric Rna

The ongoing COVID-19/Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2) pandemic has become a significant threat to public health and has hugely impacted societies globally. Targeting conserved SARS-CoV-2 RNA structures and sequences essential for viral genome translation is a novel approach to inhibit viral infection and progression. This new pharmacological modality compasses two classes of RNA-targeting molecules: 1) synthetic small molecules that recognize secondary or tertiary RNA structures and 2) antisense oligonucleotides (ASOs) that recognize the RNA primary sequence. These molecules can also serve as a “bait” fragment in RNA degrading chimeras to eliminate the viral RNA genome. This new type of chimeric RNA degrader is recently named ribonuclease targeting chimera or RIBOTAC. This review paper summarizes the sequence conservation in SARS-CoV-2 and the current development of RNA-targeting molecules to combat this virus. These RNA-binding molecules will also serve as an emerging class of antiviral drug candidates that might pivot to address future viral outbreaks.

Small molecules that selectively block RNA binding of HIV-1 rev protein inhibit rev function and viral production

Cell ◽  
1993 ◽  
Vol 74 (6) ◽  
pp. 969-978 ◽  
Author(s):  
Maria L. Zapp ◽  
Seth Stern ◽  
Michael R. Green
Keyword(s):  
Small Molecules ◽  
Rna Binding ◽  
Viral Production ◽  
Hiv 1 ◽  
Rev Protein

scholarly journals Small Molecule-Inducible RNA-Targeting Systems for Temporal Control of RNA Regulation

2020 ◽  
Author(s):  
Simone Rauch ◽  
Krysten A. Jones ◽  
Bryan Dickinson
Keyword(s):  
Gene Expression ◽  
Small Molecule ◽  
Rna Binding ◽  
Effector Proteins ◽  
Dependent Manner ◽  
Rna Regulation ◽  
Biosensor System ◽  
Gene Expression Control ◽  
Rna Targeting ◽  
Target Transcript

<div>All aspects of mRNA lifetime and function, including its stability, translational to protein, and trafficking through the cell, are tightly regulated through coordinated post-transcriptional modifications and interactions with a multitude of effector proteins. Despite the increasing recognition of RNA regulation as a critical layer of mammalian gene expression control and its increasing excitement as a therapeutic target, tools to study and control RNA regulatory mechanisms with temporal precision in their endogenous environment are lacking. Here, we present small molecule-inducible RNA-targeting effectors based on our previously-developed CRISPR/Cas-inspired RNA targeting system (CIRTS). The CIRTS biosensor system is based on guide RNA (gRNA)-dependent RNA binding domains that interact with a target transcript using Watson-Crick-Franklin base pair interactions. Addition of a small molecule recruits an RNA effector to the target transcript, thereby eliciting a local effect on the transcript. In this work, we showcase that these CIRTS biosensors can trigger inducible RNA editing, degradation, or translation on target transcripts in a small molecule-dependent manner. We further go on to show that the new CIRTS editor can induce RNA base editing in a small molecule-dependent manner in vivo. Collectively this work provides a useful new set of tools to probe the dynamics of RNA regulatory systems and a new approach to control gene expression at the RNA level.</div>

scholarly journals Type III CRISPR-Cas systems generate cyclic oligoadenylate second messengers to activate Csm6 RNases

2017 ◽  
Author(s):  
Ole Niewoehner ◽  
Carmela Garcia-Doval ◽  
Jakob T. Rostøl ◽  
Christian Berk ◽  
Frank Schwede ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Rna Binding ◽  
Second Messengers ◽  
Allosteric Activation ◽  
Conceptual Similarity ◽  
Type Iii ◽  
Rna Transcripts ◽  
Rna Targeting ◽  
Target Rna

ABSTRACTIn many prokaryotes, type III CRISPR–Cas systems detect and degrade invasive genetic elements by an RNA-guided, RNA-targeting multisubunit interference complex that possesses dual RNase and DNase activities. The CRISPR-associated protein Csm6 additionally contributes to interference by functioning as a standalone ribonuclease that degrades invader RNA transcripts, but the mechanism linking invader sensing to Csm6 activity is not understood. Here we show that Csm6 proteins are activated through a second messenger generated by the type III interference complex. Upon target RNA binding by the type III interference complex, the Cas10 subunit converts ATP into a cyclic oligoadenylate product, which allosterically activates Csm6 by binding to its CARF domain. CARF domain mutations that abolish allosteric activation inhibit Csm6 activity in vivo, and mutations in the Cas10 Palm domain phenocopy loss of Csm6. Together, these results point to a hitherto unprecedented mechanism for regulation of CRISPR interference that bears striking conceptual similarity to oligoadenylate signalling in mammalian innate immunity.

scholarly journals Discovery of RNA Binding Small Molecules Using Small Molecule Microarrays

2016 ◽  
pp. 157-175 ◽  
Author(s):  
Colleen M. Connelly ◽  
Fardokht A. Abulwerdi ◽  
John S. Schneekloth
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Rna Binding

A Light-Up Strategy with Aggregation-Induced Emission for Identification of HIV-I RNA-Binding Small Molecules

2020 ◽  
Vol 92 (19) ◽  
pp. 13532-13538
Author(s):  
Jun Li ◽  
Yao-Yao Fan ◽  
Man Wang ◽  
Hui-Ling Duan ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Small Molecules ◽  
Rna Binding ◽  
Aggregation Induced Emission

Exploring the interaction of phenothiazinium dyes methylene blue, new methylene blue, azure A and azure B with tRNAPhe: spectroscopic, thermodynamic, voltammetric and molecular modeling approach

2017 ◽  
Vol 19 (9) ◽  
pp. 6636-6653 ◽  
Author(s):  
Puja Paul ◽  
Soumya Sundar Mati ◽  
Subhash Chandra Bhattacharya ◽  
Gopinatha Suresh Kumar
Keyword(s):  
Methylene Blue ◽  
Molecular Modeling ◽  
Small Molecules ◽  
Azure A ◽  
Modeling Approach ◽  
Azure B ◽  
Rna Targeting

RNA targeting by small molecules.

scholarly journals Target-Directed Approaches for Screening Small Molecules against RNA Targets

2020 ◽  
Vol 25 (8) ◽  
pp. 869-894 ◽  
Author(s):  
Hafeez S. Haniff ◽  
Laurent Knerr ◽  
Jonathan L. Chen ◽  
Matthew D. Disney ◽  
Helen L. Lightfoot
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Drug Targets ◽  
Industrial Development ◽  
Rna Binding ◽  
Cellular Functions ◽  
Rna Molecules ◽  
The Face ◽  
Rna Binders ◽  
The Right

RNA molecules have a variety of cellular functions that can drive disease pathologies. They are without a doubt one of the most intriguing yet controversial small-molecule drug targets. The ability to widely target RNA with small molecules could be revolutionary, once the right tools, assays, and targets are selected, thereby defining which biomolecules are targetable and what constitutes drug-like small molecules. Indeed, approaches developed over the past 5–10 years have changed the face of small molecule–RNA targeting by addressing historic concerns regarding affinity, selectivity, and structural dynamics. Presently, selective RNA–protein complex stabilizing drugs such as branaplam and risdiplam are in clinical trials for the modulation of SMN2 splicing, compounds identified from phenotypic screens with serendipitous outcomes. Fully developing RNA as a druggable target will require a target engagement-driven approach, and evolving chemical collections will be important for the industrial development of this class of target. In this review we discuss target-directed approaches that can be used to identify RNA-binding compounds and the chemical knowledge we have today of small-molecule RNA binders.

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