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

PROTACs: past, present and future

“…Strategy that recruit ribonuclease against an RNA of interest via chemically induced proximity for RNA degradation is a rapidly-developing area. 126 Recently, the Disney lab identified that dovitinib, a Receptor Tyrosine Kinase (RTK) Inhibitor, also binds to a functional site in the oncogenic microRNA precursor Pre-miR-21 with a K d of 3 mM. They converted dovitinib into an RNA degrader, 127 or ribonuclease targeting chimera (RIBOTAC), which is a chimeric small molecule that also recruits ribonuclease L (RNase L) by using a previously reported small-molecule activator.…”

Proximity-Based Modalities for Biology and Medicine

“…For example, ribonucleasetargeting chimeras (RiboTACs) recruit ribonucleases to degrade RNA, 133−136 which expands the target space of induced proximity to RNA and brings the potential to target RNA by recruiting other cellular factors, such as adenosine deaminases, deadenylating enzymes, and terminal U transferase. 137 CRISPR-Cas9, as one of the most popular gene editing tools, is also a proximity-based technology. The guide RNA is a bifunctional molecule consisting of a crRNA sequence and a tracrRNA sequence that bind specifically to a target DNA sequence and recruit the Cas9 nuclease, respectively, therefore allowing precise DNA cutting by Cas9.…”

“…With induced proximity modality growing at an ever-faster speed, the field is expanding with respect to not only chemical space but also biological space. For example, ribonuclease-targeting chimeras (RiboTACs) recruit ribonucleases to degrade RNA, − which expands the target space of induced proximity to RNA and brings the potential to target RNA by recruiting other cellular factors, such as adenosine deaminases, deadenylating enzymes, and terminal U transferase . CRISPR-Cas9, as one of the most popular gene editing tools, is also a proximity-based technology.…”

Environmentally sensitive fluorescent nucleoside analogues as probes for nucleic acid – protein interactions: molecular design and biosensing applications

“…Therefore, it is not surprising that the development and refinement of methods for studying these interactions have become a problem of pivotal importance in many areas of fundamental biological and biomedical research. Besides that, such methods are of high value for drug discovery, where the possibility of targeted pharmacological modulation of nucleic acidprotein interactions has been studied intensively in the context of the development of new therapeutics for a number of diseases [13][14][15][16][17].…”