Alternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA

TitleAlternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA
Publication TypeJournal Article
Year of Publication2022
AuthorsGhosh, A, Pandey, SPrakash, Ansari, AHussain, Sundar, JSeematti, Singh, P, Khan, Y, Ekka, MKrishna, Chakraborty, D, Maiti, S
JournalNucleic Acids Research
Date PublishedJAN
Type of ArticleArticle
AbstractMALAT1, 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.
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)16.917
Divison category: 
Biochemical Sciences

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