02061nas a2200193   4500008004100000022001400041245008600055210006900141260000800210300001200218490000700230520140400237100001801641700002701659700001501686700002801701700001701729856012101746       2022                        eng d  a2162-253100aSmall molecule quercetin binds MALAT1 triplex and modulates its cellular function0 aSmall molecule quercetin binds MALAT1 triplex and modulates its   cDEC  a241-2560 v303 a<p>
	The triple-helix structure at the 30 end of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non -cod-ing 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 calo-rimetry, we observed that quercetin binds to the MALAT1 triplex with a stoichiometry of 1:1 and Kd 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, tran-scriptome-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 ther-apeutics or as a chemical tool to understand MALAT1 func-tions.</p>
1 aRakheja, Isha1 aAnsari, Asgar, Hussain1 aRay, Arjun1 aJoshi, Dheeraj, Chandra1 aMaiti, Souvi  uhttps://library.ncl.res.in/content/small-molecule-quercetin-binds-malat1-triplex-and-modulates-its-cellular-function