Search results for "RNA Splicing"
showing 10 items of 109 documents
Drosophila Muscleblind Is Involved in troponin T Alternative Splicing and Apoptosis
2008
Background: Muscleblind-like proteins (MBNL) have been involved in a developmental switch in the use of defined cassette exons. Such transition fails in the CTG repeat expansion disease myotonic dystrophy due, in part, to sequestration of MBNL proteins by CUG repeat RNA. Four protein isoforms (MblA-D) are coded by the unique Drosophila muscleblind gene. Methodology/Principal Findings: We used evolutionary, genetic and cell culture approaches to study muscleblind (mbl) function in flies. The evolutionary study showed that the MblC protein isoform was readily conserved from nematods to Drosophila, which suggests that it performs the most ancestral muscleblind functions. Overexpression of MblC…
SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes
2021
Abstract Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome—the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal sub-complexes such as SF3B1 and the large splicing cofact…
Classes of non-conventional tetraspanins defined by alternative splicing
2019
AbstractTetraspanins emerge as a family of membrane proteins mediating an exceptional broad diversity of functions. The naming refers to their four transmembrane segments, which define the tetraspanins‘ typical membrane topology. In this study, we analyzed alternative splicing of tetraspanins. Besides isoforms with four transmembrane segments, most mRNA sequences are coding for isoforms with one, two or three transmembrane segments, representing structurally mono-, di- and trispanins. Moreover, alternative splicing may alter transmembrane topology, delete parts of the large extracellular loop, or generate alternative N- or C-termini. As a result, we define structure-based classes of non-con…
A characterization of regular circular languages generated by marked splicing systems
2009
AbstractSplicing systems are generative devices of formal languages, introduced by Head in 1987 to model biological phenomena on linear and circular DNA molecules. A splicing system is defined by giving an initial set I and a set R of rules. Some unanswered questions are related to the computational power of circular splicing systems. In particular, a still open question is to find a characterization of circular languages generated by finite circular splicing systems (i.e., circular splicing systems with both I and R finite sets). In this paper we introduce a special class of the latter systems named marked systems. We prove that a marked system S generates a regular circular language if an…
The mitochondrial genome of Schizosaccharomyces pombe. Stimulation of intra-chromosomal recombination in Escherichia coli by the gene product of the …
1991
The open reading frame of the first intron of the mitochondrial cox1 gene (cox1I1) was expressed in Escherichia coli. The putative intron-encoded protein stimulated the formation of intra-chromosomal lac +-recombinants about threefold. No stimulation was found when the reading frame was inserted in the opposite direction, or when it was interrupted by a deletion. The intronic open reading frame did not complement recA − or recB − mutants of E. coli. In S. pombe, elimination of this intron did not abolish homologous recombination in mitochondria. A possible role of the recombinase activity in yeast mitochondria will be discussed.
The polypyrimidine tract-binding protein (PTB) is involved in the post-transcriptional regulation of human inducible nitric oxide synthase expression.
2006
Human inducible nitric oxide synthase (iNOS) expression is regulated by transcriptional and post-transcriptional mechanisms. We have recently shown that the multifunctional RNA-binding proteins KH-type splicing regulatory protein and tristetraprolin are critically involved in the post-transcriptional regulation of human iNOS expression. Several reports have shown that KH-type splicing regulatory protein colocalizes with the polypyrimidine tract-binding protein (PTB), and both RNA-binding proteins seem to interact with the same mRNAs. Therefore we analyzed the involvement of PTB in human iNOS expression. In human DLD-1 cells, cytokine incubation necessary to induce iNOS expression did not ch…
Anything but Ordinary - Emerging Splicing Mechanisms in Eukaryotic Gene Regulation.
2021
Splicing of precursor mRNAs (pre-mRNA) is an important step during eukaryotic gene expression. The identification of the actual splice sites and the proper removal of introns are essential for the production of the desired mRNA isoforms and their encoded proteins. While the basic mechanisms of splicing regulation are well understood, recent work has uncovered a growing number of noncanonical splicing mechanisms that play key roles in the regulation of gene expression. In this review, we summarize the current principles of splicing regulation, including the impact of cis and trans regulatory elements, as well as the influence of chromatin structure, transcription, and RNA modifications. We f…
Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity
2012
International audience; The rod-derived cone viability factors, RdCVF and RdCVF2, have potential therapeutical interests for the treatment of inherited photoreceptor degenerations. In the mouse lacking Nxnl2, the gene encoding RdCVF2, the progressive decline of the visual performance of the cones in parallel with their degeneration, arises due to the loss of trophic support from RdCVF2. In contrary, the progressive loss of rod visual function of the Nxnl2-/- mouse results from a decrease in outer segment length, mediated by a cell autonomous mechanism involving the putative thioredoxin protein RdCVF2L, the second spliced product of the Nxnl2 gene. This novel signaling mechanism extends to o…
NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning
2020
© 2020 Rathore et al. This article is distributed exclusively by the RNASociety for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.
2021
The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…