Search results for "silencing"
showing 10 items of 253 documents
Myotonic dystrophy associated expanded CUG repeat muscleblind positive ribonuclear foci are not toxic to Drosophila
2005
Myotonic dystrophy type 1 is an autosomal dominant disorder associated with the expansion of a CTG repeat in the 3 0 untranslated region (UTR) of the DMPK gene. Recent data suggest that pathogenesis is predominantly mediated by a gain of function of the mutant transcript. In patients, these expanded CUG repeat-containing transcripts are sequestered into ribonuclear foci that also contain the muscleblind-like proteins. To provide further insights into muscleblind function and the pathogenesis of myotonic dystrophy, we generated Drosophila incorporating CTG repeats in the 3 0 -UTR of a reporter gene. As in patients, expanded CUG repeats form discrete ribonuclear foci in Drosophila muscle cell…
Let it flow: Morpholino knockdown in zebrafish embryos reveals a pro-angiogenic effect of the metalloprotease meprin alpha2.
2010
BACKGROUND: Meprin metalloproteases are thought to be involved in basic physiological functions such as cell proliferation and tissue differentiation. However, the specific functions of these enzymes are still ambiguous, although a variety of growth factors and structural proteins have been identified as meprin substrates. The discovery of meprins alpha(1), alpha(2) and beta in teleost fish provided the basis for uncovering their physiological functions by gene silencing in vivo. METHODOLOGY/PRINCIPAL FINDINGS: A Morpholino knockdown in zebrafish embryos targeting meprin alpha(1) and beta mRNA caused defects in general tissue differentiation. But meprin alpha(2) morphants were affected more…
Inactivation of PadR, the repressor of the phenolic acid stress response, by molecular interaction with Usp1, a universal stress protein from Lactoba…
2009
ABSTRACT The phenolic acid decarboxylase gene padA is involved in the phenolic acid stress response (PASR) in gram-positive bacteria. In Lactobacillus plantarum , the padR gene encodes the negative transcriptional regulator of padA and is cotranscribed with a downstream gene, usp1 , which encodes a putative universal stress protein (USP), Usp1, of unknown function. The usp1 gene is overexpressed during the PASR. However, the role and the mechanism of action of the USPs are unknown in gram-positive bacteria. Therefore, to gain insights into the role of USPs in the PASR; (i) a usp1 deletion mutant was constructed; (ii) the two genes padR and usp1 were coexpressed with padA under its own promo…
Functional characterization of the enhancer blocking element of the sea urchin early histone gene cluster reveals insulator properties and three esse…
2000
Insulator elements can be functionally identified by their ability to shield promoters from regulators in a position-dependent manner or their ability to protect adjacent transgenes from position effects. We have previously reported the identification of a 265 bp sns DNA fragment at the 3' end of the sea urchin H2A early histone gene that blocked expression of a reporter gene in transgenic embryos when placed between the enhancer and the promoter. Here we show that sns interferes with enhancer-promoter interaction in a directional manner. When sns is placed between the H2A modulator and the inducible tet operator, the modulator is barred from interaction with the basal promoter. However, th…
Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376D TARDBP mutation
2022
Abstract Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons. There is no treatment for this disease that affects the ability to move, eat, speak and finally breathe, causing death. In an Italian family, a heterozygous pathogenic missense variant has been previously discovered in Exon 6 of the gene TARDBP encoding the TAR DNA-binding protein 43 protein. Here, we developed a potential therapeutic tool based on allele-specific small interfering RNAs for familial amyotrophic lateral sclerosis with the heterozygous missense mutation c.1127G>A. We designed a small interfering RNA that was able to diminish specifically the express…
Musashi-2 contributes to myotonic dystrophy muscle dysfunction by promoting excessive autophagy through miR-7 biogenesis repression
2021
Skeletal muscle symptoms strongly contribute to mortality of myotonic dystrophy type 1 (DM1) patients. DM1 is a neuromuscular genetic disease caused by CTG repeat expansions that, upon transcription, sequester the Muscleblind-like family of proteins and dysregulate alternative splicing of hundreds of genes. However, mis-splicing does not satisfactorily explain muscle atrophy and wasting, and several other contributing factors have been suggested, including hyperactivated autophagy leading to excessive catabolism. MicroRNA ( miR ) -7 has been demonstrated to be necessary and sufficient to repress the autophagy pathway in cell models of the disease, but the origin of its low levels in DM1 was…
Varjosta valokeilaan : kriittisiä diskurssianalyyseja huonosta johtamisesta
2015
The aim of this dissertation is to qualitatively describe and explain bad leader- ship and the role of the bad leader within. The dissertation consists of five orig- inal articles and the introductory section. The study is based on the foundation formed by research on bad leadership and research on discourse analysis. The focus is on the role of language in the construction, reconstruction and mainte- nance of meanings. The first of the articles contains the description of the discursive approach applied in the studies. This approach is implemented in the four remaining arti- cles, with analyzed samples of 430 media texts, a published research report (95 p.) and over 3 hours of transcribed …
Inactivation of a small heat shock protein affects cell morphology and membrane fluidity in Lactobacillus plantarum WCFS1.
2011
A small heat shock gene of Lactobacillus plantarum strain WCFS1 was deleted using a Cre-lox based system. Compared to the wild type, the ∆hsp 18.55 mutant strain displayed a similar growth rate when cultivated either under optimal temperature or under different stress conditions such as heat, low pH and salt stress. However, a longer lag phase was observed when the ∆hsp 18.55 mutant strain was cultivated under short intense heat stress (50 °C). This suggests that the hsp 18.55 gene of L. plantarum may be involved in recovery of L. plantarum stressed cells in the early stage of high temperature stress. In addition, morphology of the mutant cells, investigated by scanning electron microscopy,…
The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells
2020
Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting E…
Mechanism of the Antiretroviral Effect of dsRNA
1994
The development of AIDS seems to be linked to an impairment of processes which are induced or activated by double-stranded RNA (dsRNA), such as the biosynthesis of interferon (IFN), production of 2′,5′-oligoadenylate (2-5A), ribonuclease L (RNase L) activity and different cell-mediated immune functions. A restriction of available bioactive dsRNA (or of dsRNA-dependent enzymes) may play an important role in the disease progression. The results summarized in this review show that defects in dsRNA-dependent pathways exhibited by AIDS patients can be reversed, at least in part, by exogenously supplied dsRNA.