RNA and Proteins: Mutual Respect

Hall, Kathleen B.

doi:10.12688/f1000research.10572.1

Cited by 10 publications

(7 citation statements)

References 95 publications

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“…The authors concluded that base pairs in the RNA hairpins are progressively disrupted by stacking interactions with the aromatic side chains, accompanied by hydrogen bonding with surrounding basic residues. This combination of aromatic and basic side chains, found in other RNA binding proteins (83), seems to offer a flexible yet energetically favorable interaction surface for single-stranded RNA. Importantly, side chains on the exposed surface of CspA are dynamic (84), but are stabilized upon binding to the RNA hairpin (82).…”

Section: Introductionmentioning

confidence: 91%

Proteins That Chaperone RNA Regulation

Woodson¹,

Panja²,

Santiago-Frangos

2018

Microbiol Spectr

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RNA-binding proteins chaperone the biological functions of non-coding RNA by reducing RNA misfolding, improving matchmaking between regulatory RNA and targets, and exerting quality control over RNP biogenesis. Recent studies of E. coli CspA, HIV NCp and E. coli Hfq, are beginning to show how RNA-binding proteins remodel RNA structures. These different protein families use common strategies for disrupting or annealing RNA double helices, which can be used to understand the mechanisms by which proteins chaperone RNA-dependent regulation in bacteria.

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Section: Introductionmentioning

confidence: 91%

Proteins That Chaperone RNA Regulation

Woodson¹,

Panja²,

Santiago-Frangos

2018

Microbiol Spectr

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“…Finally, we also observed an upregulation of snoRNAs, a type of small noncoding RNAs implicated in a broad range of biological functions including the regulation of ribosomes and of fundamental cancer proteins by directly binding to them or affecting their posttranslational modifications or their RNA molecules (43)(44)(45)(46)(47)(48). The role of snoRNAs in lymphoid neoplasms has not yet been fully explored (49,50) and they appear largely reduced in tumors compared with normal tissue counterparts (49).…”

Section: Discussionmentioning

confidence: 78%

The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents

Spriano

Chung

Gaudio

et al. 2019

Clinical Cancer Research

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Purpose: Transcription factors are commonly deregulated in cancer, and they have been widely considered as difficult to target due to their nonenzymatic mechanism of action. Altered expression levels of members of the ETStranscription factors are often observed in many different tumors, including lymphomas. Here, we characterized two small molecules, YK-4-279 and its clinical derivative, TK-216, targeting ETS factors via blocking the proteinprotein interaction with RNA helicases, for their antilymphoma activity. Experimental Design: The study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination; validation experiments on in vivo models; and transcriptome and coimmunoprecipitation experiments. Results: YK-4-279 and TK-216 demonstrated an antitumor activity across several lymphoma cell lines, which we validated in vivo. We observed synergistic activity when YK-4-279 and TK-216 were combined with the BCL2 inhibitor venetoclax and with the immunomodulatory drug lenalidomide. YK-4-279 and TK-216 interfere with protein interactions of ETS family members SPIB, in activated B-cell-like type diffuse large B-cell lymphomas, and SPI1, in germinal center B-cell-type diffuse large B-cell lymphomas. Conclusions: The ETS inhibitor YK-4-279 and its clinical derivative TK-216 represent a new class of agents with in vitro and in vivo antitumor activity in lymphomas. Although their detailed mechanism of action needs to be fully defined, in DLBCL they might act by targeting subtype-specific essential transcription factors.

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“…The last two decades have seen the development of high-throughput gene expression profiling technologies, including DNA microarrays and RNA-sequencing (RNA-seq), leading to an increased focus on RNA and its interacting partners. Indeed, increasing numbers of RNA–protein ( 1 ), RNA–small molecule (e.g. riboswitches ( 2 )) and RNA–RNA interactions (e.g.…”

Section: Introductionmentioning

confidence: 99%

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions

Phillips

Butt

Henderson

et al. 2018

Nucleic Acids Research

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We are just beginning to unravel the myriad of interactions in which non-coding RNAs participate. The intricate RNA interactome is the foundation of many biological processes, including bacterial virulence and human disease, and represents unexploited resources for the development of potential therapeutic interventions. However, identifying specific associations of a given RNA from the multitude of possible binding partners within the cell requires robust high-throughput systems for their rapid screening. Here, we present the first demonstration of functional-RNA arrays as a novel platform technology designed for the study of such interactions using immobilized, active RNAs. We have generated high-density RNA arrays by an innovative method involving surface-capture of in vitro transcribed RNAs. This approach has significant advantages over existing technologies, particularly in its versatility in regards to binding partner character. Indeed, proof-of-principle application of RNA arrays to both RNA–small molecule and RNA–RNA pairings is demonstrated, highlighting their potential as a platform technology for mapping RNA-based networks and for pharmaceutical screening. Furthermore, the simplicity of the method supports greater user-accessibility over currently available technologies. We anticipate that functional-RNA arrays will find broad utility in the expanding field of RNA characterization.

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RNA and Proteins: Mutual Respect

Cited by 10 publications

References 95 publications

Proteins That Chaperone RNA Regulation

Proteins That Chaperone RNA Regulation

The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions

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