scholarly journals Alternative splicing of a Drosophila tropomyosin gene generates muscle tropomyosin isoforms with different carboxy-terminal ends.

1984 ◽  
Vol 4 (12) ◽  
pp. 2828-2836 ◽  
Author(s):  
G S Basi ◽  
M Boardman ◽  
R V Storti
Keyword(s):  
Alternative Splicing ◽  
Transcription Unit ◽  
Protein Isoforms ◽  
Tropomyosin Isoforms ◽  
Exon Splicing ◽  
Muscle Tropomyosin ◽  
Specific Mrnas ◽  
Carboxy Terminal ◽  
Splicing Patterns ◽  
I Gene

The muscle tropomyosin I (mTm I) gene from Drosophila melanogaster has been analyzed and shown to express a complex transcription unit consisting of two sets of tissue-specific mRNAs. A 1.3- and 1.6-kilobase set of mRNAs is expressed during myogenesis in embryos, and in myogenic cell cultures. The mRNAs encode a 34,000-dalton muscle tropomyosin isoform. The same mTm I gene expresses a different set of 1.7- and 1.9-kilobase mRNAs in thoracic flight muscle tissue of the adult. The thorax RNAs encode a new tropomyosin isoform resolved on two-dimensional gels. The structure of the gene has been determined, and we show that the embryonic and thoracic mRNAs are generated by alternative splicing. The alternate exon splicing patterns determine a different 27 amino acids at the carboxy-terminal end of the two tropomyosin isoforms. These results show that the carboxy-terminal domain of tropomyosin is highly regulated in determining tropomyosin function. The results also show that contractile protein isoforms can be generated by single as well as multiple genes.

Alternative splicing of a Drosophila tropomyosin gene generates muscle tropomyosin isoforms with different carboxy-terminal ends

1984 ◽  
Vol 4 (12) ◽  
pp. 2828-2836
Author(s):  
G S Basi ◽  
M Boardman ◽  
R V Storti
Keyword(s):  
Alternative Splicing ◽  
Transcription Unit ◽  
Protein Isoforms ◽  
Tropomyosin Isoforms ◽  
Exon Splicing ◽  
Muscle Tropomyosin ◽  
Specific Mrnas ◽  
Carboxy Terminal ◽  
Splicing Patterns ◽  
I Gene

The muscle tropomyosin I (mTm I) gene from Drosophila melanogaster has been analyzed and shown to express a complex transcription unit consisting of two sets of tissue-specific mRNAs. A 1.3- and 1.6-kilobase set of mRNAs is expressed during myogenesis in embryos, and in myogenic cell cultures. The mRNAs encode a 34,000-dalton muscle tropomyosin isoform. The same mTm I gene expresses a different set of 1.7- and 1.9-kilobase mRNAs in thoracic flight muscle tissue of the adult. The thorax RNAs encode a new tropomyosin isoform resolved on two-dimensional gels. The structure of the gene has been determined, and we show that the embryonic and thoracic mRNAs are generated by alternative splicing. The alternate exon splicing patterns determine a different 27 amino acids at the carboxy-terminal end of the two tropomyosin isoforms. These results show that the carboxy-terminal domain of tropomyosin is highly regulated in determining tropomyosin function. The results also show that contractile protein isoforms can be generated by single as well as multiple genes.

scholarly journals Integrative Visual Analysis of the Effects of Alternative Splicing on Protein Domain Interaction Networks

2008 ◽  
Vol 5 (2) ◽  
Author(s):  
Dorothea Emig ◽  
Melissa S. Cline ◽  
Karsten Klein ◽  
Anne Kunert ◽  
Petra Mutzel ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Protein Interactions ◽  
Visual Analysis ◽  
Protein Isoforms ◽  
Interaction Networks ◽  
Protein Domain ◽  
Domain Interaction ◽  
Exon Arrays ◽  
Exon Expression ◽  
Splicing Patterns

SummaryProteins and their interactions are essential for the functioning of all organisms and for understanding biological processes. Alternative splicing is an important molecular mechanism for increasing the protein diversity in eukaryotic cells. Splicing events that alter the protein structure and the domain composition can be responsible for the regulation of protein interactions and the functional diversity of different tissues. Discovering the occurrence of splicing events and studying protein isoforms have become feasible using Affymetrix Exon Arrays. Therefore, we have developed the versatile Cytoscape plugin DomainGraph that allows for the visual analysis of protein domain interaction networks and their integration with exon expression data. Protein domains affected by alternative splicing are highlighted and splicing patterns can be compared.

scholarly journals Alternative Splicing Variants of IκBβ Establish Differential NF-κB Signal Responsiveness in Human Cells

1998 ◽  
Vol 18 (5) ◽  
pp. 2596-2607 ◽  
Author(s):  
Fuminori Hirano ◽  
Mirra Chung ◽  
Hirotoshi Tanaka ◽  
Naoki Maruyama ◽  
Isao Makino ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Processing ◽  
Abundant Species ◽  
Human Cells ◽  
Protein Isoforms ◽  
Activation Mechanism ◽  
Proteolytic Degradation ◽  
Phosphorylation Sites ◽  
Splicing Variants ◽  
Carboxy Terminal

ABSTRACT To release transcription factor NF-κB into the nucleus, the mammalian IκB molecules IκBα and IκBβ are inactivated by phosphorylation and proteolytic degradation. Both proteins contain conserved signal-responsive phosphorylation sites and have conserved ankyrin repeats. To confer specific physiological functions to members of the NF-κB/Rel family, the different IκB molecules could vary in their specific NF-κB/Rel factor binding activities and could respond differently to activation signals. We have demonstrated that both mechanisms apply to differential regulation of NF-κB function by IκBβ relative to IκBα. Via alternative RNA processing, human IκBβ gives rise to different protein isoforms. IκBβ1 and IκBβ2, the major forms in human cells, differ in their carboxy-terminal PEST sequences. IκBβ2 is the most abundant species in a number of human cell lines tested, whereas IκBβ1 is the only form detected in murine cells. These isoforms are indistinguishable in their binding preferences to cellular NF-κB/Rel homo- and heterodimers, which are distinct from those of IκBα, and both are constitutively phosphorylated. In unstimulated B cells, however, IκBβ1, but not IκBβ2, is found in the nucleus. Furthermore, the two forms differ markedly in their efficiency of proteolytic degradation after stimulation with several inducing agents tested. While IκBβ1 is nearly as responsive as IκBα, indicative of a shared activation mechanism, IκBβ2 is only weakly degraded and often not responsive at all. Alternative splicing of the IκBβ pre-mRNA may thus provide a means to selectively control the amount of IκBβ-bound NF-κB heteromers to be released under NF-κB stimulating conditions.

Alternative Splicing of SDIR1 Gene in Arabidopsis thaliana (Cruciferae)

2010 ◽  
Vol 32 (2) ◽  
pp. 141-146 ◽  
Author(s):  
Xiao-Lu WU ◽  
Xiao-Qian TANG ◽  
Li-Xia YU ◽  
You-Lin YAO ◽  
Bo YAN
Keyword(s):  
Arabidopsis Thaliana ◽  
Alternative Splicing ◽  
I Gene

scholarly journals PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Dawei Chen ◽  
Zhenguo Zhao ◽  
Lu Chen ◽  
Qinghua Li ◽  
Jixue Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Alternative Splicing ◽  
Protein Function ◽  
Vital Role ◽  
Normal Tissues ◽  
Mechanistic Analysis ◽  
Highly Correlated ◽  
Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

scholarly journals The Alcohol Dehydrogenase Gene Is Nested in the outspread Locus of Drosophila melanogaster

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 897-911 ◽  
Author(s):  
S McNabb ◽  
S Greig ◽  
T Davis
Keyword(s):  
Drosophila Melanogaster ◽  
Alcohol Dehydrogenase ◽  
Pcr Amplification ◽  
Transcription Unit ◽  
Adjacent Gene ◽  
Dehydrogenase Gene ◽  
Chromosomal Breakpoints ◽  
Splicing Patterns ◽  
Somatic Musculature

Abstract This report describes the structure and expression of the outspread (osp) gene of Drosophila melanogaster. Previous work showed that chromosomal breakpoints associated with mutations of the osp locus map to both sides of the alcohol dehydrogenase gene (Adh), suggesting that Adh and the adjacent gene Adh' are nested in osp. We extended a chromosomal walk and mapped additional osp mutations to define the maximum molecular limit of osp as 119 kb. We identified a 6-kb transcript that hybridizes to osp region DNA and is altered or absent in osp mutants. Accumulation of this RNA peaks during embryonic and pupal periods. The osp cDNAs comprise two distinct classes based on alternative splicing patterns. The 5′ end of the longest cDNA was extended by PCR amplification. When hybridized to the osp walk, the 5′ extension verifies that Adh and Adh' are nested in osp and shows that osp has a transcription unit of ≥74 kb. In situ hybridization shows that osp is expressed both maternally and zygotically. In the ovary, osp is transcribed in nurse cells and localized in the oocyte. In embryos, expression is most abundant in the developing visceral and somatic musculature.

scholarly journals The evolution of alternative splicing in glioblastoma under therapy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lin Wang ◽  
Karin Shamardani ◽  
Husam Babikir ◽  
Francisca Catalan ◽  
Takahide Nejo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Standard Of Care ◽  
Surface Proteins ◽  
Adult Brain ◽  
Primary Tumors ◽  
Cell Therapies ◽  
Therapeutic Development ◽  
Human Gbm ◽  
Tissue Specimens ◽  
Splicing Patterns

Abstract Background Alternative splicing is a rich source of tumor-specific neoantigen targets for immunotherapy. This holds promise for glioblastomas (GBMs), the most common primary tumors of the adult brain, which are resistant to standard-of-care therapy. Although most clinical trials enroll patients at recurrence, most preclinical studies have been done with specimens from primary disease. There are limited expression data from GBMs at recurrence and surprisingly little is known about the evolution of splicing patterns under therapy. Result We profile 37 primary-recurrent paired human GBM specimens via RNA sequencing. We describe the landscape of alternative splicing in GBM at recurrence and contrast that to primary and non-malignant brain-tissue specimens. By screening single-cell atlases, we identify cell-type-specific splicing patterns and novel splicing events in cell-surface proteins that are suitable targets for engineered T cell therapies. We identify recurrent-specific isoforms of mitogen-activated kinase pathway genes that enhance invasiveness and are preferentially expressed by stem-like cells. Conclusion These studies shed light on gene expression in recurrent GBM and identify novel targets for therapeutic development.

scholarly journals Neurodegenerative diseases: a hotbed for splicing defects and the potential therapies

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Dunhui Li ◽  
Craig Stewart McIntosh ◽  
Frank Louis Mastaglia ◽  
Steve Donald Wilton ◽  
May Thandar Aung-Htut
Keyword(s):  
Alternative Splicing ◽  
Neurodegenerative Diseases ◽  
Messenger Rna ◽  
Muscular Atrophy ◽  
Single Gene ◽  
Synaptic Function ◽  
Coding Regions ◽  
Splicing Defects ◽  
The Impact ◽  
Splicing Patterns

AbstractPrecursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA). This process is highly regulated and can be highly flexible through a process known as alternative splicing, which allows for several transcripts to arise from a single gene, thereby greatly increasing genetic plasticity and the diversity of proteome. Alternative splicing is particularly prevalent in neuronal cells, where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis, migration and synaptic function. The continuous changes in splicing patterns and a high demand on many cis- and trans-splicing factors contribute to the susceptibility of neuronal tissues to splicing defects. The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function. Several of the most common neurodegenerative diseases involve some form of splicing defect(s), such as Alzheimer’s disease, Parkinson’s disease and spinal muscular atrophy. Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics. Here we review our current understanding of the effects alternative splicing has on neuronal differentiation, neuronal migration, synaptic maturation and regulation, as well as the impact on neurodegenerative diseases. We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.

Computation-assisted targeted proteomics of alternative splicing protein isoforms in the human heart

2021 ◽  
Vol 154 ◽  
pp. 92-96
Author(s):  
Yu Han ◽  
Silas D. Wood ◽  
Julianna M. Wright ◽  
Vishantie Dostal ◽  
Edward Lau ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Human Heart ◽  
Protein Isoforms ◽  
Targeted Proteomics

scholarly journals Expression of Alternatively Spliced Sodium Channel α-Subunit Genes

2004 ◽  
Vol 279 (44) ◽  
pp. 46234-46241 ◽  
Author(s):  
Christopher K. Raymond ◽  
John Castle ◽  
Philip Garrett-Engele ◽  
Christopher D. Armour ◽  
Zhengyan Kan ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Genomic Sequence ◽  
Molecular Medicine ◽  
Primate Model ◽  
Α Subunit ◽  
Alternatively Spliced ◽  
Splicing Patterns

Molecular medicine requires the precise definition of drug targets, and tools are now in place to provide genome-wide information on the expression and alternative splicing patterns of any known gene. DNA microarrays were used to monitor transcript levels of the nine well-characterized α-subunit sodium channel genes across a broad range of tissues from cynomolgus monkey, a non-human primate model. Alternative splicing of human transcripts for a subset of the genes that are expressed in dorsal root ganglia, SCN8A (Nav1.6), SCN9A (Nav1.7), and SCN11A (Nav1.9) was characterized in detail. Genomic sequence analysis among gene family paralogs and between cross-species orthologs suggested specific alternative splicing events within transcripts of these genes, all of which were experimentally confirmed in human tissues. Quantitative PCR revealed that certain alternative splice events are uniquely expressed in dorsal root ganglia. In addition to characterization of human transcripts, alternatively spliced sodium channel transcripts were monitored in a rat model for neuropathic pain. Consistent down-regulation of all transcripts was observed, as well as significant changes in the splicing patterns of SCN8A and SCN9A.

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