被撤回的出版物: Alternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA (Publication with Expression of Concern. See vol. 50, pg. 4199, 2022) (Retracted article. See AUG, 2023)

MALAT1, 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.

Automated summary

The study identified three conserved and stable rG4 structures in the 3' region of MALAT1 that regulate alternative splicing, and demonstrated the importance of rG4s in the localization of NCL and NPM to nuclear speckles. Disruption of rG4 in MALAT1 resulted in altered pre-mRNA splicing of endogenous genes, similar to NCL knockdown.