RNAi of arcRNA hsrω affects sub-cellular localization of Drosophila FUS to drive neurodiseases

Piccolo, Luca Lo; Yamaguchi, Masamitsu

doi:10.1016/j.expneurol.2017.03.011

Cited by 41 publications

(42 citation statements)

References 41 publications

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“…8C). Surprisingly, levels of transcripts for none of the known omega speckle associated hnRNPs and those whose intracellular distribution is affected in hsrω 66 cells (Lakhotia et al 2012; Mallik and Lakhotia 2011; Piccolo et al 2017; Piccolo and Yamaguchi 2017; Singh and Lakhotia 2015) were significantly altered in any of the three mutant genotypes examined. However, heph and sm , which encode members of the hnRNP-L family, were down-regulated in hsrω 66 Hsp90GFP homozygotes.…”

Section: Resultsmentioning

confidence: 89%

“…8D, E). These two hnRNP family proteins, like the other hnRNPs (Lakhotia 2011; Piccolo et al 2017; Piccolo and Yamaguchi 2017), are expected to be associated with the omega speckles although this has not yet been experimentally demonstrated.…”

Section: Resultsmentioning

confidence: 98%

“…The globally expressed hsrω gene produces multiple nuclear and cytoplasmic non-coding transcripts (Lakhotia 2011, 2016; Lakhotia 2017). The larger nuclear hsrω transcripts are essential for the assembly of nucleoplasmic omega speckles harbouring a variety of hnRNPs and some other RNA binding proteins so that in the absence or reduced or elevated levels of the hsrω nuclear transcripts, the associated hnRNPs and other proteins lose their characteristic speckled nucleoplasmic distribution, which affects their sub-cellular localization, dynamic mobility and availability (Lakhotia 2017; Mallik and Lakhotia 2011; Piccolo et al 2017; Piccolo and Yamaguchi 2017; Prasanth et al 2000; Singh and Lakhotia 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Activity at the hsrω locus affects poly-ADP-ribosylation of hnRNPs (Ji and Tulin 2009, 2013), which in turn can affect many downstream events like splicing and turnover of RNA. Down-regulation of hsrω transcripts also causes hnRNPs like dFUS (Caz) to move to cytoplasm where it shows greater interaction with dFMRP (Piccolo and Yamaguchi 2017). The TDPH/TDP-43 also physically associates with hsr ω nuclear RNAs (Piccolo et al 2018) and alterations in poly-ADP-ribose binding affects its liquid-phase separation properties and sub-cellular localization (McGurk et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Since none of these genes were affected in ω or Hsp90GFP single mutants or in hsrω Hsp90GFP/+ heterozygotes, interactions between these two gene products appear to be very sensitive to their relative levels. Depletion of hsrω transcripts affects intra-cellular dynamics of the diverse hnRNPs (Lakhotia et al 2012;Piccolo et al 2017; Piccolo and Yamaguchi 2017) while Hsp83/Hsp90 is known to bind (Sawarkar et al 2012; Singh and Lakhotia 2015; Tariq et al 2009) with promoters of several highly down-regulated genes in Sp/CyO; hsrω 66 Hsp90GFP larvae. Hsp90 and a variety of hnRNPs also directly interact and regulate a wide variety of cellular activities (Chen et al 2007; Chi et al 2018; Creugny et al 2018; Ford et al 2002; Grammatikakis et al 1999; Jinwal et al 2012; Lackie et al 2017; Youn et al 2018; Zhang et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Over-expression of Hsp83 in grossly depletedhsrωlncRNA background causes synthetic lethality andl(2)glphenocopy inDrosophila

Ray

Acharya

Shambhavi

et al. 2018

Preprint

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We examined interactions between Hsp83 and hsrω lncRNAs in hsrω 66 Hsp90GFP homozygotes, which almost completely lack hsrω lncRNAs but over-express Hsp83. All +/+; hsrω 66 Hsp90GFP progeny died before third instar. Rare Sp/CyO; hsrω 66 Hsp90GFP reached third instar stage but phenocopied l(2)gl mutants, dying after prolonged larval life, becoming progressively bulbous and transparent with enlarged brain. Additionally, ventral ganglia were elongated. However, hsrω 66 Hsp90GFP/TM6B heterozygotes, carrying +/+ or Sp/CyO second chromosomes, developed normally. Total RNA sequencing (+/+, +/+; hsrω 66 /hsrω 66 , Sp/CyO; hsrω 66 /hsrω 66 , +/+; Hsp90GFP/Hsp90GFP, and Sp/CyO; hsrω 66 Hsp90GFP/hsrω 66 Hsp90GFP late third instar larvae) revealed similar effects on many genes in hsrω 66 and Hsp90GFP homozygotes. Besides additive effect on many of them, numerous additional genes were affected in Sp/CyO; hsrω 66 Hsp90GFP larvae, with l(2)gl and several genes regulating CNS being highly down-regulated in surviving Sp/CyO; hsrω 66 Hsp90GFP larvae, but not in hsrω 66 or Hsp90GFP single mutants. Hsp83 binds at these gene promoters. Several omega speckle associated hnRNPs too may bind with these genes and transcripts. Hsp83-hnRNP interactions are also known. Thus, elevated Hsp83 in altered hnRNP distribution and dynamics, following absence of hsrω lncRNAs and omega speckles, background can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumor suppressor gene like l(2)gl. 0 1 5

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Over-expression of Hsp83 in grossly depletedhsrωlncRNA background causes synthetic lethality andl(2)glphenocopy inDrosophila

Ray

Acharya

Shambhavi

et al. 2018

Preprint

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Long noncoding RNA‐dependent methylation of nonhistone proteins

et al. 2021

Self Cite

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In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNAdependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N-MTase activity of EZH2, protein arginine-MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/ nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders.

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Drosophila Models to Study Long Noncoding RNAs Related to Neurological Disorders

Muraoka

Yamaguchi

2020

RNA Technologies

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RNAi of arcRNA hsrω affects sub-cellular localization of Drosophila FUS to drive neurodiseases

Cited by 41 publications

References 41 publications

Over-expression of Hsp83 in grossly depletedhsrωlncRNA background causes synthetic lethality andl(2)glphenocopy inDrosophila

Over-expression of Hsp83 in grossly depletedhsrωlncRNA background causes synthetic lethality andl(2)glphenocopy inDrosophila

Long noncoding RNA‐dependent methylation of nonhistone proteins

Drosophila Models to Study Long Noncoding RNAs Related to Neurological Disorders

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