scholarly journals Bidirectional Analysis of Cryba4-Crybb1 Nascent Transcription and Nuclear Accumulation of Crybb3 mRNAs in Lens Fibers

2019 ◽  
Vol 60 (1) ◽  
pp. 234 ◽  
Author(s):  
Saima Limi ◽  
Yilin Zhao ◽  
Peng Guo ◽  
Melissa Lopez-Jones ◽  
Deyou Zheng ◽  
...  
Keyword(s):  
Nuclear Accumulation ◽  
Lens Fibers

Half- Sandwich cyclopentadienylruthenium(II) Complexes: A New Antimalarial Chemotype

2020 ◽  
Author(s):  
Sofia Alexandra Milheiro ◽  
Joana Gonçalves ◽  
Ricardo Lopes ◽  
Margarida Madureira ◽  
Lis Lobo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Blood Stage ◽  
Nuclear Accumulation ◽  
Selective Absorption ◽  
Asexual Parasite ◽  
Single Digit ◽  
Liver Stage ◽  
Dual Stage ◽  
Fluorescent Compounds ◽  
Half Sandwich

<p><a>A small library of “half-sandwich” cyclopentadienylruthenium(II) compounds of general formula [(</a>η<sup>5</sup>-C<sub>5</sub>R<sub>5</sub>)Ru(PPh<sub>3</sub>)(N-N)][PF<sub>6</sub>], a scaffold hitherto unfeatured in the toolbox of antiplasmodials, was screened for activity against the blood stage of CQ-sensitive 3D7-GFP, CQ-resistant Dd2 and artemisinin-resistant IPC5202 <i>Plasmodium falciparum</i> strains, and the liver stage of <i>P. berghei</i>. The best performing compounds displayed dual-stage activity, with single-digit nM IC<sub>50</sub> values against blood stage malaria parasites, nM activity against liver stage parasites, and residual cytotoxicity against mammalian cells (HepG2, Huh7). Parasitic absorption/distribution of 7-nitrobenzoxadiazole-appended fluorescent compounds <b>Ru4</b> and <b>Ru5</b> was investigated by confocal fluorescence microscopy, revealing parasite-selective absorption in infected erythrocytes and nuclear accumulation of both compounds. The lead compound <b>Ru2</b> impaired asexual parasite differentiation, exhibiting fast parasiticidal activity against both ring and trophozoite stages of a synchronized <i>P. falciparum</i> 3D7 strain. These results point to cyclopentadienylruthenium(II) complexes as a highly promising chemotype for the development of dual-stage antiplasmodials.</p>

scholarly journals TheDrosophila double-timeSMutation Delays the Nuclear Accumulation ofperiodProtein and Affects the Feedback Regulation ofperiodmRNA

2001 ◽  
Vol 21 (18) ◽  
pp. 7117-7126 ◽  
Author(s):  
Shu Bao ◽  
Jason Rihel ◽  
Ed Bjes ◽  
Jin-Yuan Fan ◽  
Jeffrey L. Price
Keyword(s):  
Feedback Regulation ◽  
Nuclear Accumulation

scholarly journals C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons

2021 ◽  
Author(s):  
Eun Seon Kim ◽  
Chang Geon Chung ◽  
Jeong Hyang Park ◽  
Byung Su Ko ◽  
Sung Soon Park ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Accumulation ◽  
Heterozygous Mutation ◽  
Pathological Feature ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Drosophila Model ◽  
Post Transcriptional Regulation

Abstract RNA-binding proteins (RBPs) play essential roles in diverse cellular processes through post-transcriptional regulation of RNAs. The subcellular localization of RBPs is thus under tight control, the breakdown of which is associated with aberrant cytoplasmic accumulation of nuclear RBPs such as TDP-43 and FUS, well-known pathological markers for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Here, we report in Drosophila model for ALS/FTD that nuclear accumulation of a cytoplasmic RBP, Staufen, may be a new pathological feature. We found that in Drosophila C4da neurons expressing PR36, one of the arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in Importin- and RNA-dependent manner. Notably, expressing Staufen with exogenous NLS—but not with mutated endogenous NLS—potentiated PR-induced dendritic defect, suggesting that nuclear-accumulated Staufen can enhance PR toxicity. PR36 expression increased Fibrillarin staining in the nucleolus, which was enhanced by heterozygous mutation of stau (stau+/−), a gene that codes Staufen. Furthermore, knockdown of fib, which codes Fibrillarin, exacerbated retinal degeneration mediated by PR toxicity, suggesting that increased amount of Fibrillarin by stau+/− is protective. Stau+/− also reduced the amount of PR-induced nuclear-accumulated Staufen and mitigated retinal degeneration and rescued viability of flies expressing PR36. Taken together, our data show that nuclear accumulation of Staufen in neurons may be an important pathological feature contributing to the pathogenesis of ALS/FTD.

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