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Affecting RNA biology genome-wide by binding small molecules and chemically induced proximity. | LitMetric

Affecting RNA biology genome-wide by binding small molecules and chemically induced proximity.

Curr Opin Chem Biol

Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458 USA. Electronic address:

Published: June 2021

AI Article Synopsis

Article Abstract

The ENCODE and genome-wide association projects have shown that much of the genome is transcribed into RNA and much less is translated into protein. These and other functional studies suggest that the druggable transcriptome is much larger than the druggable proteome. This review highlights approaches to define druggable RNA targets and structure-activity relationships across genomic RNA. Binding compounds can be identified and optimized into structure-specific ligands by using sequence-based design with various modes of action, for example, inhibiting translation or directing pre-mRNA splicing outcomes. In addition, strategies to direct protein activity against an RNA of interest via chemically induced proximity is a burgeoning area that has been validated both in cells and in preclinical animal models, and we describe that it may allow rapid access to new avenues to affect RNA biology. These approaches and the unique modes of action suggest that more RNAs are potentially amenable to targeting than proteins.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264282PMC
http://dx.doi.org/10.1016/j.cbpa.2021.03.006DOI Listing

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