PMID- 36284512
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221028
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 30
DP  - 2022 Dec 13
TI  - Small molecule quercetin binds MALAT1 triplex and modulates its cellular 
      function.
PG  - 241-256
LID - 10.1016/j.omtn.2022.09.016 [doi]
AB  - The triple-helix structure at the 3' end of metastasis-associated lung 
      adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA, has been considered 
      to be a target for modulating the oncogenic functions of MALAT1. This study 
      examines the binding of quercetin-a known triplex binding molecule-to the MALAT1 
      triplex. By employing UV-visible spectroscopy, circular dichroism spectroscopy, 
      and isothermal titration calorimetry, we observed that quercetin binds to the 
      MALAT1 triplex with a stoichiometry of 1:1 and K (d) of 495 +/- 61 nM, along with a 
      negative change in free energy, indicating a spontaneous interaction. Employing 
      real-time PCR measurements, we observed around 50% downregulation of MALAT1 
      transcript levels in MCF7 cells, and fluorescence in situ hybridization (FISH) 
      experiments showed concomitantly reduced levels of MALAT1 in nuclear speckles. 
      This interaction is likely a result of a direct interaction between the molecule 
      and the RNA, as indicated by a transcription-stop experiment. Further, 
      transcriptome-wide analysis of alternative splicing changes induced by quercetin 
      revealed modulation of MALAT1 downstream genes. Collectively, our study shows 
      that quercetin strongly binds to the MALAT1 triplex and modulates its functions. 
      It can thus be used as a scaffold for further development of therapeutics or as a 
      chemical tool to understand MALAT1 functions.
CI  - (c) 2022 The Author(s).
FAU - Rakheja, Isha
AU  - Rakheja I
AD  - Chemical and Systems Biology Unit, Council of Scientific and Industrial 
      Research-Institute of Genomics & Integrative Biology, New Delhi 110025, India.
AD  - Academy of Scientific & Innovative Research (AcSIR), CSIR-Human Resource 
      Development Centre, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 
      201002, India.
FAU - Ansari, Asgar Hussain
AU  - Ansari AH
AD  - Chemical and Systems Biology Unit, Council of Scientific and Industrial 
      Research-Institute of Genomics & Integrative Biology, New Delhi 110025, India.
AD  - Academy of Scientific & Innovative Research (AcSIR), CSIR-Human Resource 
      Development Centre, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 
      201002, India.
FAU - Ray, Arjun
AU  - Ray A
AD  - Department of Computational Biology, Indraprastha Institute of Information 
      Technology Delhi (IIIT-Delhi), Okhla Industrial Estate, Phase III, New Delhi 
      110020, India.
FAU - Chandra Joshi, Dheeraj
AU  - Chandra Joshi D
AD  - Chemical and Systems Biology Unit, Council of Scientific and Industrial 
      Research-Institute of Genomics & Integrative Biology, New Delhi 110025, India.
AD  - Academy of Scientific & Innovative Research (AcSIR), CSIR-Human Resource 
      Development Centre, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 
      201002, India.
FAU - Maiti, Souvik
AU  - Maiti S
AD  - Chemical and Systems Biology Unit, Council of Scientific and Industrial 
      Research-Institute of Genomics & Integrative Biology, New Delhi 110025, India.
AD  - Institute of Genomics and Integrative Biology (IGIB)-National Chemical Laboratory 
      (NCL) Joint Center, Council of Scientific and Industrial Research-NCL, Pune 
      411008, India.
AD  - Academy of Scientific & Innovative Research (AcSIR), CSIR-Human Resource 
      Development Centre, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 
      201002, India.
LA  - eng
PT  - Journal Article
DEP - 20220923
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC9576543
OTO - NOTNLM
OT  - MALAT1
OT  - MT: Oligonucleotides: Therapies and Applications
OT  - RNA FISH
OT  - in silico docking
OT  - isothermal titration calorimetry
OT  - quercetin
OT  - small-molecule binding
OT  - triple helix
COIS- The authors declare there are no competing interests.
EDAT- 2022/10/27 06:00
MHDA- 2022/10/27 06:01
PMCR- 2022/09/23
CRDT- 2022/10/26 02:03
PHST- 2021/12/22 00:00 [received]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/10/26 02:03 [entrez]
PHST- 2022/10/27 06:00 [pubmed]
PHST- 2022/10/27 06:01 [medline]
PHST- 2022/09/23 00:00 [pmc-release]
AID - S2162-2531(22)00259-1 [pii]
AID - 10.1016/j.omtn.2022.09.016 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2022 Sep 23;30:241-256. doi: 10.1016/j.omtn.2022.09.016. 
      eCollection 2022 Dec 13.