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Identification of RNA aptamer which specifically interacts with PtdIns(3)P

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Title: Identification of RNA aptamer which specifically interacts with PtdIns(3)P
Authors: Donia, Thoria Browse this author
Jyoti, Bala Browse this author
Suizu, Futoshi Browse this author →KAKEN DB
Hirata, Noriyuki Browse this author
Tanaka, Tsutomu Browse this author
Ishigaki, Satoko Browse this author
Thomas, Pranzatelli J. F. Browse this author
Nio-Kobayashi, Junko Browse this author →KAKEN DB
Iwanaga, Toshihiko Browse this author →KAKEN DB
Chiorini, John A. Browse this author
Noguchi, Masayuki Browse this author →KAKEN DB
Keywords: Phosphoinositide
RNA aptamer
Molecular imaging
Issue Date: 10-Sep-2019
Publisher: Elsevier
Journal Title: Biochemical and biophysical research communications
Volume: 517
Issue: 1
Start Page: 146
End Page: 154
Publisher DOI: 10.1016/j.bbrc.2019.07.034
PMID: 31351587
Abstract: The phosphinositide Ptdlns(3)P plays an important role in autophagy; however, the detailed mechanism of its activity remains unclear. Here, we used a Systematic Evolution of Ligands by EXponential enrichment (SELEX) screening approach to identify an RNA aptamer of 40 nucleotides that specifically recognizes and binds to intracellular lysosomal Ptdlns(3)P. Binding occurs in a magnesium concentration- and pH-dependent manner, and consequently inhibits autophagy as determined by LC3II/I conversion, p62 degradation, formation of LC3 puncta, and lysosomal accumulation of Phafin2. These effects in turn inhibited lysosomal acidification, and the subsequent hydrolytic activity of cathepsin D following induction of autophagy. Given the essential role of Ptdlns(3)P as a key targeting molecule for autophagy induction, identification of this novel Ptdlns(3)P RNA aptamer provides new opportunities for investigating the biological functions and mechanisms of phosphoinositides. (C) 2019 The Authors. Published by Elsevier Inc.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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