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

Autor:	Jennifer Seematti Sundar, Yasmeen Khan, Souvik Maiti, Arpita Ghosh, Mary Krishna Ekka, Debojyoti Chakraborty, Asgar Hussain Ansari, Praveen Singh, Satyaprakash Pandey
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Gene knockdown MALAT1 Nucleophosmin AcademicSubjects/SCI00010 Alternative splicing RNA-Binding Proteins Biology G-quadruplex Phosphoproteins Cell biology G-Quadruplexes Alternative Splicing RNA splicing Genetics RNA and RNA-protein complexes Humans RNA Long Noncoding Nucleolin Gene HeLa Cells
Zdroj:	Nucleic Acids Research
ISSN:	1362-4962 0305-1048
Popis:	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 RNA-G-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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed31c628bccdd28f05e0a6090db2f138 http://europepmc.org/articles/PMC8754661 Zobrazit plný text záznamu