01709nas a2200241   4500008004100000022001400041245008900055210006900144260000800213300001200221490000700233520090000240100001801140700002701158700002701185700003101212700001901243700001801262700002401280700002701304700001801331856011801349       2022                        eng d  a0305-104800aAlternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA0 aAlternative splicing modulation mediated by Gquadruplex structur  cJAN  a378-3960 v503 aMALAT1, an abundant lncRNA specifically localized to nuclear speckles, regulates alternative-splicing (AS). The molecular basis of its role in AS remains poorly understood. Here, we report three conserved, thermodynamically stable, parallel RNAG-quadruplexes (rG4s) present in the 3' region of MALAT1 which regulates this function. Using rG4 domain-specific RNA-pull-down followed by mass-spectrometry, RNA-immuno-precipitation, and imaging, we demonstrate the rG4 dependent localization of Nucleolin (NCL) and Nucleophosmin (NPM) to nuclear speckles. Specific G-to-A mutations that abolish rG4 structures, result in the localization loss of both the proteins from speckles. Functionally, disruption of rG4 in MALAT1 phenocopies NCL knockdown resulting in altered pre-mRNA splicing of endogenous genes. These results reveal a central role of rG4s within the 3' region of MALAT1 orchestrating AS.1 aGhosh, Arpita1 aPandey, Satya, Prakash1 aAnsari, Asgar, Hussain1 aSundar, Jennifer, Seematti1 aSingh, Praveen1 aKhan, Yasmeen1 aEkka, Mary, Krishna1 aChakraborty, Debojyoti1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/alternative-splicing-modulation-mediated-g-quadruplex-structures-malat1-lncrna