Alternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA
| Title | Alternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Ghosh, A, Pandey, SPrakash, Ansari, AHussain, Sundar, JSeematti, Singh, P, Khan, Y, Ekka, MKrishna, Chakraborty, D, Maiti, S |
| Journal | Nucleic Acids Research |
| Volume | 50 |
| Issue | 1 |
| Pagination | 378-396 |
| Date Published | JAN |
| Type of Article | Article |
| ISSN | 0305-1048 |
| Abstract | 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. |
| DOI | 10.1093/nar/gkab1066 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 16.917 |
Divison category:
Biochemical Sciences
Add new comment