Search results for " alternative splicing"
showing 7 items of 7 documents
Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform
2017
Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-Δe8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a specific siRNA that spares the Hipk2-Δe8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant-negative effect of Hipk2-FL over the Δe8 isoform. From this observation, we sought to take advantage and assessed the therape…
The Compass-like Locus, Exclusive to the Ambulacrarians, Encodes a Chromatin Insulator Binding Protein in the Sea Urchin Embryo
2013
Chromatin insulators are eukaryotic genome elements that upon binding of specific proteins display barrier and/or enhancer-blocking activity. Although several insulators have been described throughout various metazoans, much less is known about proteins that mediate their functions. This article deals with the identification and functional characterization in Paracentrotus lividus of COMPASS-like (CMPl), a novel echinoderm insulator binding protein. Phylogenetic analysis shows that the CMPl factor, encoded by the alternative spliced Cmp/Cmpl transcript, is the founder of a novel ambulacrarian-specific family of Homeodomain proteins containing the Compass domain. Specific association of CMPl…
β1D Integrin Inhibits Cell Cycle Progression in Normal Myoblasts and Fibroblasts
1998
Integrins are alphabeta heterodimeric transmembrane receptors involved in the regulation of cell growth and differentiation. The beta1 integrin subunit is widely expressed in vivo and is represented by four alternatively spliced cytoplasmic domain isoforms. beta1D is a muscle-specific variant of beta1 integrin and a predominant beta1 isoform in striated muscles. In the present study we showed that expression of the exogenous beta1D integrin in C2C12 myoblasts and NIH 3T3 or REF 52 fibroblasts inhibited cell proliferation. Unlike the case of the common beta1A isoform, adhesion of beta1D-transfected C2C12 myoblasts specifically via the expressed integrin did not activate mitogen-activated pro…
Photosensitive Alternative Splicing of the Circadian Clock Gene timeless Is Population Specific in a Cold-Adapted Fly, Drosophila montana.
2018
To function properly, organisms must adjust their physiology, behavior and metabolism in response to a suite of varying environmental conditions. One of the central regulators of these changes is organisms' internal circadian clock, and recent evidence has suggested that the clock genes are also important in the regulation of seasonal adjustments. In particular, thermosensitive splicing of the core clock gene <i>timeless</i> in a cosmopolitan fly, <i>Drosophila melanogaster</i> , has implicated this gene to be involved in thermal adaptation. To further investigate this link we examined the splicing of <i>timeless</i> in a northern malt fly species, <i&…
Vezatin, a novel transmembrane protein, bridges myosin VIIA to the cadherin-catenins complex
2000
International audience; Defects in myosin VIIA are responsible for deafness in the human and mouse. The role of this unconventional myosin in the sensory hair cells of the inner ear is not yet understood. Here we show that the C-terminal FERM domain of myosin VIIA binds to a novel transmembrane protein, vezatin, which we identi®ed by a yeast two-hybrid screen. Vezatin is a ubiquitous protein of adherens cell±cell junctions, where it interacts with both myosin VIIA and the cadherin±catenins complex. Its recruitment to adherens junctions implicates the C-terminal region of a-catenin. Taken together, these data suggest that myosin VIIA, anchored by vezatin to the cadherin±catenins complex, cre…
Alternative splicing of SMPD1 in human sepsis.
2015
Acid sphingomyelinase (ASM or sphingomyelin phosphodiesterase, SMPD) activity engages a critical role for regulation of immune response and development of organ failure in critically ill patients. Beside genetic variation in the human gene encoding ASM (SMPD1), alternative splicing of the mRNA is involved in regulation of enzymatic activity. Here we show that the patterns of alternatively spliced SMPD1 transcripts are significantly different in patients with systemic inflammatory response syndrome and severe sepsis/septic shock compared to control subjects allowing discrimination of respective disease entity. The different splicing patterns might contribute to the better understanding of th…
Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy
2021
Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSALR mouse model and patient-d…