A cross-nearest neighbor/Monte Carlo algorithm for single-molecule localization microscopy defines interactions between p53, Mdm2, and MEG3.
Algorithms
Humans
Image Processing, Computer-Assisted
/ methods
Microscopy, Fluorescence
/ methods
Monte Carlo Method
Protein Interaction Domains and Motifs
Proto-Oncogene Proteins c-mdm2
/ genetics
RNA, Long Noncoding
/ genetics
Single Molecule Imaging
/ methods
Tumor Suppressor Protein p53
/ genetics
computational biology
image analysis
long noncoding RNA (long ncRNA)
microscopy
mouse double minute 2 homolog
p53
single-molecule localization microscopy
stochastic optical reconstruction microscopy
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
16
06
2020
revised:
15
02
2021
accepted:
11
03
2021
pubmed:
17
3
2021
medline:
24
8
2021
entrez:
16
3
2021
Statut:
ppublish
Résumé
The functions of long noncoding (lnc)RNAs, such as MEG3, are defined by their interactions with other RNAs and proteins. These interactions, in turn, are shaped by their subcellular localization and temporal context. Therefore, it is important to be able to analyze the relationships of lncRNAs while preserving cellular architecture. The ability of MEG3 to suppress cell proliferation led to its recognition as a tumor suppressor. MEG3 has been proposed to activate p53 by disrupting the interaction of p53 with mouse double minute 2 homolog (Mdm2). To test this mechanism in the native cellular context, we employed two-color direct stochastic optical reconstruction microscopy, a single-molecule localization microscopy technique, to detect and quantify the localizations of p53, Mdm2, and MEG3 in U2OS cells. We developed a new cross-nearest neighbor/Monte Carlo algorithm to quantify the association of these molecules. Proof of concept for our method was obtained by examining the association between FKBP1A and mTOR, MEG3 and p53, and Mdm2 and p53. In contrast to previous models, our data support a model in which MEG3 modulates p53 independently of the interaction with Mdm2.
Identifiants
pubmed: 33722609
pii: S0021-9258(21)00318-5
doi: 10.1016/j.jbc.2021.100540
pmc: PMC8038948
pii:
doi:
Substances chimiques
MEG3 non-coding RNA, human
0
RNA, Long Noncoding
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100540Subventions
Organisme : NCI NIH HHS
ID : R01 CA193520
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062472
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027931
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007540
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no conflicts of interest in regards to this manuscript.
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