Dataset Information

RNA pull-down-Confocal Nanoscanning (RP-CONA) detects quercetin as pri-miR-7/HuR interaction inhibitor that decreases a-Synuclein levels

ABSTRACT: RNA-protein interactions are central to all gene expression processes and contribute to a variety of human diseases. Therapeutic approaches targeting RNA-protein interactions have shown promising effects on some diseases that are previously regarded as ‘incurable’. Here we developed a fluorescent on-bead screening platform: RNA Pull-Down-COnfocal NAnoscanning (RP-CONA), to identify RNA-protein interaction modulators in eukaryotic cell extracts. Using RP-CONA, we identified small molecules that disrupt the interaction between HuR, an inhibitor of brain-enriched miR-7 biogenesis, and the conserved terminal loop of pri-miR-7-1. Importantly, miR-7’s primary target is an mRNA of α-Synuclein, which contributes to the aetiology of Parkinson’s disease. Our method identified a natural product quercetin as a molecule able to upregulate cellular miR-7 levels and downregulate the expression of α-Synuclein. This opens up new therapeutic avenues towards treatment of Parkinson’s disease as well as provides a novel methodology to search for modulators of RNA-protein interaction.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Parkinson's Disease

SUBMITTER: Gracjan Michlewski

LAB HEAD: Gracjan Michlewski

PROVIDER: PXD025617 | Pride | 2022-02-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Zhu_2021_GM_pri-miR-7-1-CTL_RP-SMS__vs-__quercetin.raw	Raw
	Zhu_2021_GM_pri-miR-7-1-CTL_RP-SMS__vs-__quercetin.zip	Other

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Publications

RNA pull-down confocal nanoscanning (RP-CONA) detects quercetin as pri-miR-7/HuR interaction inhibitor that decreases α-synuclein levels.

Zhu Siran S Choudhury Nila Roy NR Rooney Saul S Pham Nhan T NT Koszela Joanna J Kelly David D Spanos Christos C Rappsilber Juri J Auer Manfred M Michlewski Gracjan G

Nucleic acids research 20210601 11

RNA-protein interactions are central to all gene expression processes and contribute to a variety of human diseases. Therapeutic approaches targeting RNA-protein interactions have shown promising effects on some diseases that are previously regarded as 'incurable'. Here, we developed a fluorescent on-bead screening platform, RNA Pull-Down COnfocal NAnoscanning (RP-CONA), to identify RNA-protein interaction modulators in eukaryotic cell extracts. Using RP-CONA, we identified small molecules that ...[more]

PMID: 34107032

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