Search results for "RNA splicing"
showing 9 items of 109 documents
Depletion ofL-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes
2012
PMCID: PMC3494587
Alternative splicing regulation by Muscleblind proteins: from development to disease.
2011
Regulated use of exons in pre-mRNAs, a process known as alternative splicing, strongly contributes to proteome diversity. Alternative splicing is finely regulated by factors that bind specific sequences within the precursor mRNAs. Members of the Muscleblind (Mbl) family of splicing factors control critical exon use changes during the development of specific tissues, particularly heart and skeletal muscle. Muscleblind homologs are only found in metazoans from Nematoda to mammals. Splicing targets and recognition mechanisms are also conserved through evolution. In this recognition, Muscleblind CCCH-type zinc finger domains bind to intronic motifs in pre-mRNA targets in which the protein can e…
A ceRNA analysis on LMNA gene focusing on the Hutchinson-Gilford progeria syndrome
2013
Background: Hutchinson-Gilford progeria syndrome is a rare dominant human disease of genetic origin. The average life expectancy is about 20 years, patients’ life quality is still very poor and no efficient therapy has yet been developed. It is caused by mutation of the LMNA gene, which results in accumulation in the nuclear membrane of a particular splicing form of Lamin-A called progerin. The mechanism by which progerin perturbs cellular homeostasis and leads to the symptoms is still under debate. Micro-RNAs are able to negatively regulate transcription by coupling with the 3’ UnTranslated Region of messenger RNAs. Several Micro-RNAs recognize the same 3’ UnTranslated Region and each Micr…
Genetic and Chemical Modifiers Of A CUG Toxicity Model in Drosophila
2007
Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL) proteins contributing to myotonic dystrophy 1 (DM1). To understand this toxic RNA gain-of-function mechanism we developed a Drosophila model expressing 60 pure and 480 interrupted CUG repeats in the context of a non-translatable RNA. These flies reproduced aspects of the DM1 pathology, most notably nuclear accumulation of CUG transcripts, muscle degeneration, splicing misregulation, and diminished Muscleblind function in vivo. Reduced Muscleblind activity was evident from the sensitivity of CUG-induced phenotypes to a decrease in muscleblind genetic dosage and rescue by MBNL1 expression, and furthe…
In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models
2011
6 pages, 5 figures. PMID:21730182[PubMed] PMCID: PMC3141925[Available on 2012/1/19]
Deregulated Splicing Is a Major Mechanism of RNA-Induced Toxicity in Huntington's Disease.
2019
Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant…
Regulation of PTHrP and PTH/PTHrP receptor by extracellular Ca2+ concentration and hormones in the breast cancer cell line 8701-BC.
2000
AbstractIt was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormonerelated peptide (PTHrP) and PTH/PTHrP receptor (PTHrPR) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrPR by breast cancer cells has been poorly investigated so far, we have chosen the 8701- BC cell line as a model system to investigate whether alterations in the extracellular Ca[2+] concentration ([Ca[2+]]) and treatment with some wellknown differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, alltrans retinoic acid and transforming growth factorβ1 might (i) modulat…
Expanded CCUG repeat RNA expression in Drosophila heart and muscle trigger Myotonic Dystrophy type 1-like phenotypes and activate autophagocytosis ge…
2016
AbstractMyotonic dystrophies (DM1–2) are neuromuscular genetic disorders caused by the pathological expansion of untranslated microsatellites. DM1 and DM2, are caused by expanded CTG repeats in the 3′UTR of the DMPK gene and CCTG repeats in the first intron of the CNBP gene, respectively. Mutant RNAs containing expanded repeats are retained in the cell nucleus, where they sequester nuclear factors and cause alterations in RNA metabolism. However, for unknown reasons, DM1 is more severe than DM2. To study the differences and similarities in the pathogenesis of DM1 and DM2, we generated model flies by expressing pure expanded CUG ([250]×) or CCUG ([1100]×) repeats, respectively, and compared …
Extracellular matrix regulation of PTHrP and PTH/PTHrP receptor in a human breast cancer cell line
1999
AbstractIt was previously reported that 8701-BC breast cancer cells express the gene for parathyroid hormone-related peptide (PTHrP) and its cognate receptor (PTHrP-R), and release immunoreactive PTHrP in the extracellular medium; it was also found that PTHrP, in turn, exerts a role on the proliferative and invasive behavior in vitro of the same cell line. On the other hand, evidence has been produced that adhesion of 8701-BC cells onto different collagen substrates influences in various ways a number of phenotypic expressions, such as cell growth, motility, invasion of reconstituted basement membrane and production of lytic enzymes of the extracellular matrix (ECM). In light of these previ…