%0 Journal Article
%T Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery
%A Alessandro Provenzani
%A Alessandro Quattrone
%A Chiara Zucal
%A Denise Sighel
%A Graziano Lolli
%A Isabelle Bonomo
%A Mariachiara Micaelli
%A Valentina Adami
%A Vito Giuseppe D¡¯Agostino
%J SLAS DISCOVERY: Advancing Life Sciences R&D
%@ 2472-5560
%D 2019
%R 10.1177/2472555218818065
%X RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA¨Cprotein interactions with small molecules is now expanding the concept of protein ¡°druggability,¡± with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein¨CRNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts
%K RBP
%K RNP
%K RNA¨Cprotein interaction
%K HTS
%K RBP targeting
%U https://journals.sagepub.com/doi/full/10.1177/2472555218818065