Drosophila oncogene Gas41 is an RNA interference modulator that intersects heterochromatin and the small interfering RNA pathway. (17th November 2014)

• Record Type: Journal Article
• Authors: Gandhi, Sumit G.; Bag, Indira; Sengupta, Saswati; Pal‐Bhadra, Manika; Bhadra, Utpal
• Is Part Of: FEBS journal. Volume 282:Number 1(2015)
• Page Start: 153
• Page End: 173
• Publication Date: 2014-11-17
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13115
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs13115-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Glioma amplified sequence41</italic> (<italic>Gas41</italic>) is a highly conserved putative transcription factor that is frequently abundant in human gliomas. <italic>Gas41</italic> shows oncogenic activity by promoting cell growth and viability. In the present study, we show that <italic>Gas41</italic> is required for proper functioning of RNA interference (RNAi) machinery in the nuclei, although three basic structural domains of RNAi components PAZ, PIWI and dsRNA with respect to binding are absent in the structural sequences. Variations of structural domains are highly conserved among prokaryotes and eukaryotes. <italic>Gas41</italic> interacts with cytological RNase III enzyme <italic>Dicer1</italic> both biochemically and genetically. However, <italic>Drosophila Gas41</italic> functions as chromatin remodeler and interacts with different heterochromatin markers and repeat‐induced transgene silencing by modulating position effect variegation. We also show that transcriptional inactive <italic>Gas41</italic> mutant interferes with the functional assembly of heterochromatin‐associated proteins, dimethylated lysine 9 of histone H3 and heterochromatic protein 1 in developing embryos. A reduction of heterochromatic markers is accompanied by the <italic>mini‐w</italic> promoter sequence in <italic>Gas41</italic> mutants. These findings suggest that <italic>Drosophila Gas41</italic> guides the repeat associated gene silencing and the <italic>Dicer1</italic> interaction, thereby depicting a new role for <italic>Gas41</italic>. <italic>Gas41</italic> is a critical RNAi component. In <italic>Drosophila</italic>, <italic> Gas41</italic> plays a dual role. On the one hand, it appears to participate with <italic>Dicer 1</italic> in the RNAi pathway and, alternatively, it also participates in repeat‐induced gene silencing by accumulating heterochromatin proteins at the <italic>mini‐w</italic> array promoters. Therefore, it represents an intriguing and apparently paradoxical new finding in RNA technology with respect to the process of heterochromatin gene silencing.</p> </abstract>