scholarly journals Srrm234, but not canonical SR and hnRNP proteins, drive inclusion of Dscam exon 9 variable exons

RNA ◽  
2019 ◽  
Vol 25 (10) ◽  
pp. 1353-1365 ◽  
Author(s):  
Pinar Ustaoglu ◽  
Irmgard U. Haussmann ◽  
Hongzhi Liao ◽  
Antonio Torres-Mendez ◽  
Roland Arnold ◽  
...  
Keyword(s):  
Hnrnp Proteins ◽  
Exon 9

scholarly journals Srrm234, but not canonical SR and hnRNP proteins drive inclusion of Dscam exon 9 variable exons

2019 ◽  
Author(s):  
Pinar Ustaoglu ◽  
Irmgard U. Haussmann ◽  
Hongzhi Liao ◽  
Antonio Torres-Mendez ◽  
Roland Arnold ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Alternative Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Main Role ◽  
Sr Protein ◽  
Exon Inclusion ◽  
Hnrnp Proteins ◽  
Exon 9

AbstractAlternative splicing of pre-mRNA is a major mechanism to diversify protein functionality in metazoans from a limited number of genes. In the Drosophila melanogaster Down Syndrome Cell Adhesion Molecule (Dscam) important for neuronal wiring up to 38,016 isoforms can be generated by mutually exclusive alternative splicing in four clusters of variable exons. However, it is not understood how a specific exon is chosen from the many variables and how variable exons are prevented from being spliced together. A main role in the regulation of Dscam alternative splicing has been attributed to RNA binding proteins, but how they impact on exon selection is not well understood. Serine-arginine-rich (SR) proteins and hnRNP proteins are the two main types of RNA binding proteins with major roles in exon definition and splice site selection. Here, we analyzed the role of SR and hnRNP proteins in Dscam exon 9 alternative splicing in mutant Drosophila melanogaster embryos because of their essential function for development. Strikingly, loss or overexpression of canonical SR and hnRNP proteins even when multiple proteins are depleted together, does not affect Dscam alternative exon selection very dramatically. Conversely, non-canonical SR protein Serine-arginine repetitive matrix 2/3/4 (Srrm234) is a main determinant of exon inclusion in Dscam exon 9 cluster. Since long-range base-pairings are absent in the exon 9 cluster, our data argue for a small complement of regulatory factors as main determinants of exon inclusion in the Dscam exon 9 cluster.

Homozygous mutation in ABCA3 Lipid-Transporter defect (EXON 9) and low level of surfactant protein C

2010 ◽  
Vol 222 (S 01) ◽  
Author(s):  
J Pöschl ◽  
P Ruef ◽  
M Griese ◽  
P Lohse ◽  
C Aslanidis ◽  
...  
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Homozygous Mutation ◽  
Surfactant Protein C ◽  
Low Level ◽  
Exon 9 ◽  
Lipid Transporter

Mutationsanalysen zur Therapieoptimierung gefordert

2010 ◽  
Vol 01 (02) ◽  
pp. 96-96
Author(s):  
Petra Eiden
Keyword(s):  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Gastrointestinale Stromatumoren ◽  
Exon 9 ◽  
Exon 11

Gastrointestinale Stromatumoren (GIST), an denen in Deutschland jährlich etwa 1250 Menschen neu erkranken, entstehen aus mesenchymalen, interstitiellen Stammzellen im Bereich des Auerbach-Plexus, weit überwiegend aufgrund spezifischer Mutationen im Gen des KIT-, seltener auch des PDGF-Rezeptors (Platelet Derived Growth Factor), die zur Selbstaktivierung der Rezeptoren führen. Die meisten KIT-Mutationen liegen im Exon 11 (ca. 65%) oder Exon 9 (ca. 15%). Da Chemo- und Strahlentherapie keine Wirksamkeit erzielen, stellte die Entwicklung der Tyrosinkinase-Inhibitoren (TKI) Imatinib und Sunitinib laut Prof. Jörg Thomas Hartmann, Tübingen, einen deutlichen Fort-schritt dar: Sie unterbrechen die Selbstaktivierung der Rezeptoren, indem sie diese in-trazellulär blockieren.

scholarly journals Screening for Plasminogen Mutations in Hereditary Angioedema Patients

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 402
Author(s):  
Henriette Farkas ◽  
Anna Dóczy ◽  
Edina Szabó ◽  
Lilian Varga ◽  
Dorottya Csuka
Keyword(s):  
Gene Mutation ◽  
Hereditary Angioedema ◽  
Unknown Origin ◽  
Factor Xii ◽  
Gene Encoding ◽  
New Techniques ◽  
Ex Post ◽  
Appropriate Therapy ◽  
Exon 9 ◽  
Serping1 Gene

Hereditary angioedema (HAE) is a rare disease belonging to the group of bradykinin-mediated angioedemas, characterized by recurring edematous episodes involving the subcutaneous and/or submucosal tissues. Most cases of HAE are caused by mutations in the SERPING1 gene encoding C1-inhibitor (C1-INH-HAE); however, mutation analysis identified seven further types of HAE: HAE with Factor XII mutation (FXII-HAE), with plasminogen gene mutation (PLG-HAE), with angiopoietin-1 gene mutation (ANGPT1-HAE), with kininogen-1 gene mutation (KNG1-HAE), with a myoferlin gene mutation (MYOF-HAE), with a heparan sulfate-glucosamine 3-sulfotransferase 6 (HS3ST6) mutation, and hereditary angioedema of unknown origin (U-HAE). We sequenced DNA samples stored from 124 U-HAE patients in the biorepository for exon 9 of the PLG gene. One of the 124 subjects carried the mutation causing a lysine to glutamic acid amino acid exchange at position 330 (K330E). Later, the same PLG mutation was identified in the patient’s son. The introduction of new techniques into genetic testing has increased the number of genes identified. As shown by this study, a biorepository creates the means for the ex-post analysis of recently identified genes in stored DNA samples of the patients. This makes the diagnosis more accurate with the possibility of subsequent family screening and the introduction of appropriate therapy.

scholarly journals Quantitative Evaluation of CFTR Pre-mRNA Splicing Dependent on the (TG)mTn Poly-Variant Tract

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 168
Author(s):  
Manuela Sterrantino ◽  
Andrea Fuso ◽  
Silvia Pierandrei ◽  
Sabina Maria Bruno ◽  
Giancarlo Testino ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Functional Effect ◽  
Transmembrane Conductance ◽  
Therapeutic Consequences ◽  
Clinical Consequences ◽  
Exon 9 ◽  
The Many ◽  
Cystic Fibrosis Transmembrane ◽  
Exon 10

Genetic analysis in cystic fibrosis (CF) is a difficult task. Within the many causes of variability and uncertainty, a major determinant is poor knowledge of the functional effect of most DNA variants of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. In turn, knowledge of the effect of a CFTR variant has dramatic diagnostic, prognostic and, in the era of CF precision medicine, also therapeutic consequences. One of the most challenging CFTR variants is the (TG)mTn haplotype, which has variable functional effect and controversial clinical consequences. The exact quantification of the anomalous splicing of CFTR exon 10 (in the HGVS name; exon 9 in the legacy name) and, consequently, of the residual wild-type functional CFTR mRNA, should be mandatory in clinical assessment of patients with potentially pathological haplotype of this tract. Here, we present a real time-based assay for the quantification of the proportion of exon 10+/exon 10− CFTR mRNA, starting from nasal brushing. Our assay proved rapid, economic and easy to perform. Specific primers used for this assay are either disclosed or commercially available, allowing any laboratory to easily perform it. A simplified analysis of the data is provided, facilitating the interpretation of the results. This method helps to enhance the comprehension of the genotype–phenotype relationship in CF and CFTR-related disorders (CFTR-RD), crucial for the diagnosis, prognosis and personalized therapy of CF.

scholarly journals Primary and Secondary Kinase Genotypes Correlate With the Biological and Clinical Activity of Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumor

2008 ◽  
Vol 26 (33) ◽  
pp. 5352-5359 ◽  
Author(s):  
Michael C. Heinrich ◽  
Robert G. Maki ◽  
Christopher L. Corless ◽  
Cristina R. Antonescu ◽  
Amy Harlow ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Clinical Results ◽  
Clinical Activity ◽  
Wild Type ◽  
Mutational Status ◽  
Imatinib Resistant ◽  
Exon 9 ◽  
Exon 11 ◽  
The Impact

PurposeMost gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor α (PDGFRA) kinases, which are imatinib targets. Sunitinib, which targets KIT, PDGFRs, and several other kinases, has demonstrated efficacy in patients with GIST after they experience imatinib failure. We evaluated the impact of primary and secondary kinase genotype on sunitinib activity.Patients and MethodsTumor responses were assessed radiologically in a phase I/II trial of sunitinib in 97 patients with metastatic, imatinib-resistant/intolerant GIST. KIT/PDGFRA mutational status was determined for 78 patients by using tumor specimens obtained before and after prior imatinib therapy. Kinase mutants were biochemically profiled for sunitinib and imatinib sensitivity.ResultsClinical benefit (partial response or stable disease for ≥ 6 months) with sunitinib was observed for the three most common primary GIST genotypes: KIT exon 9 (58%), KIT exon 11 (34%), and wild-type KIT/PDGFRA (56%). Progression-free survival (PFS) was significantly longer for patients with primary KIT exon 9 mutations (P = .0005) or with a wild-type genotype (P = .0356) than for those with KIT exon 11 mutations. The same pattern was observed for overall survival (OS). PFS and OS were longer for patients with secondary KIT exon 13 or 14 mutations (which involve the KIT-adenosine triphosphate binding pocket) than for those with exon 17 or 18 mutations (which involve the KIT activation loop). Biochemical profiling studies confirmed the clinical results.ConclusionThe clinical activity of sunitinib after imatinib failure is significantly influenced by both primary and secondary mutations in the predominant pathogenic kinases, which has implications for optimization of the treatment of patients with GIST.

scholarly journals Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms

RNA ◽  
2012 ◽  
Vol 19 (1) ◽  
pp. 96-102 ◽  
Author(s):  
S. Erkelenz ◽  
W. F. Mueller ◽  
M. S. Evans ◽  
A. Busch ◽  
K. Schoneweis ◽  
...  
Keyword(s):  
Hnrnp Proteins

scholarly journals High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
William Jacot ◽  
Caroline Mollevi ◽  
Frédéric Fina ◽  
Evelyne Lopez-Crapez ◽  
Pierre-Marie Martin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Protein Expression ◽  
Triple Negative ◽  
Breast Cancers ◽  
Pik3ca Mutations ◽  
Exon 9

Characterization and primary structure of the poly(C)-binding heterogeneous nuclear ribonucleoprotein complex K protein

1992 ◽  
Vol 12 (1) ◽  
pp. 164-171
Author(s):  
M J Matunis ◽  
W M Michael ◽  
G Dreyfuss
Keyword(s):  
Hela Cells ◽  
Mammalian Cells ◽  
Binding Proteins ◽  
Rna Binding ◽  
Consensus Sequence ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Predicted Amino Acid Sequence ◽  
Cdna Clones ◽  
Hnrnp Proteins

At least 20 major proteins make up the ribonucleoprotein (RNP) complexes of heterogeneous nuclear RNA (hnRNA) in mammalian cells. Many of these proteins have distinct RNA-binding specificities. The abundant, acidic heterogeneous nuclear RNP (hnRNP) K and J proteins (66 and 64 kDa, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) are unique among the hnRNP proteins in their binding preference: they bind tenaciously to poly(C), and they are the major oligo(C)- and poly(C)-binding proteins in human HeLa cells. We purified K and J from HeLa cells by affinity chromatography and produced monoclonal antibodies to them. K and J are immunologically related and conserved among various vertebrates. Immunofluorescence microscopy with antibodies shows that K and J are located in the nucleoplasm. cDNA clones for K were isolated, and their sequences were determined. The predicted amino acid sequence of K does not contain an RNP consensus sequence found in many characterized hnRNP proteins and shows no extensive homology to sequences of any known proteins. The K protein contains two internal repeats not found in other known proteins, as well as GlyArgGlyGly and GlyArgGlyGlyPhe sequences, which occur frequently in many RNA-binding proteins. Overall, K represents a novel type of hnRNA-binding protein. It is likely that K and J play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences.

Sign in / Sign up

Export Citation Format

Share Document