scholarly journals The alpha 1 chain of type XIII collagen consists of three collagenous and four noncollagenous domains, and its primary transcript undergoes complex alternative splicing.

1990 ◽  
Vol 265 (28) ◽  
pp. 16922-16928 ◽  
Author(s):  
T Pihlajaniemi ◽  
M Tamminen
Keyword(s):  
Alternative Splicing ◽  
Primary Transcript ◽  
Type Xiii Collagen

scholarly journals Genome-wide Analysis of Alternative Pre-mRNA Splicing

2007 ◽  
Vol 283 (3) ◽  
pp. 1229-1233 ◽  
Author(s):  
Claudia Ben-Dov ◽  
Britta Hartmann ◽  
Josefin Lundgren ◽  
Juan Valcárcel
Keyword(s):  
Alternative Splicing ◽  
Large Scale ◽  
Mrna Splicing ◽  
Diagnostic Tools ◽  
Primary Transcript ◽  
Genome Wide ◽  
Human Genes ◽  
Multicellular Organisms ◽  
Eukaryotic Genomes ◽  
Key Questions

Alternative splicing of mRNA precursors allows the synthesis of multiple mRNAs from a single primary transcript, significantly expanding the information content and regulatory possibilities of higher eukaryotic genomes. High-throughput enabling technologies, particularly large-scale sequencing and splicing-sensitive microarrays, are providing unprecedented opportunities to address key questions in this field. The picture emerging from these pioneering studies is that alternative splicing affects most human genes and a significant fraction of the genes in other multicellular organisms, with the potential to greatly influence the evolution of complex genomes. A combinatorial code of regulatory signals and factors can deploy physiologically coherent programs of alternative splicing that are distinct from those regulated at other steps of gene expression. Pre-mRNA splicing and its regulation play important roles in human pathologies, and genome-wide analyses in this area are paving the way for improved diagnostic tools and for the identification of novel and more specific pharmaceutical targets.

Cell-Cycle Dependent Alternative Splicing of the Tenascin Primary Transcript

1994 ◽  
Vol 1 (4) ◽  
pp. 307-317 ◽  
Author(s):  
Laura Borsi ◽  
Enrica Balza ◽  
Patrizia Castellani ◽  
Barbara Carnemolla ◽  
Marco Ponassi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Primary Transcript ◽  
Cycle Dependent

Control of calcitonin/calcitonin gene-related peptide pre-mRNA processing by constitutive intron and exon elements

1993 ◽  
Vol 13 (10) ◽  
pp. 5999-6011
Author(s):  
J M Yeakley ◽  
F Hedjran ◽  
J P Morfin ◽  
N Merillat ◽  
M G Rosenfeld ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Calcitonin Gene Related Peptide ◽  
Regulatory Sequences ◽  
Primary Transcript ◽  
Tissue Specific ◽  
Related Peptide ◽  
Thyroid C Cells ◽  
Calcitonin Gene ◽  
Constitutive Splicing ◽  
Specific Regulation

The calcitonin/calcitonin gene-related peptide (CGRP) primary transcript is alternatively spliced in thyroid C cells and neurons, resulting in the tissue-specific production of calcitonin and CGRP mRNAs. Analyses of mutated calcitonin/CGRP transcription units in permanently transfected cell lines have indicated that alternative splicing is regulated by a differential capacity to utilize the calcitonin-specific splice acceptor. The analysis of an extensive series of mutations suggests that tissue-specific regulation of calcitonin mRNA production does not depend on the presence of a single, unique cis-active element but instead appears to be a consequence of suboptimal constitutive splicing signals. While only those mutations that altered constitutive splicing signals affected splice choices, the action of multiple regulatory sequences cannot be formally excluded. Further, we have identified a 13-nucleotide purine-rich element from a constitutive exon that, when placed in exon 4, entirely switches splice site usage in CGRP-producing cells. These data suggest that specific exon recruitment sequences, in combination with other constitutive elements, serve an important function in exon recognition. These results are consistent with the hypothesis that tissue-specific alternative splicing of the calcitonin/CGRP primary transcript is mediated by cell-specific differences in components of the constitutive splicing machinery.

scholarly journals A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1.

1990 ◽  
Vol 10 (10) ◽  
pp. 5271-5278 ◽  
Author(s):  
I Mineo ◽  
P R Clarke ◽  
R L Sabina ◽  
E W Holmes
Keyword(s):  
Alternative Splicing ◽  
Donor Site ◽  
Specific Pattern ◽  
Splice Donor Site ◽  
Splice Donor ◽  
Primary Transcript ◽  
Exon 2 ◽  
Tissue Specific ◽  
Exon 1 ◽  
Alternatively Spliced

AMP deaminase (AMPD) is a central enzyme in eucaryotic energy metabolism, and tissue-specific as well as stage-specific isoforms are found in many vertebrates. This study demonstrates the AMPD1 gene product in rat is alternatively spliced. The second exon, a 12-base miniexon, was found to be excluded or included in a tissue-specific and stage-specific pattern. This example of cassette splicing utilizes a unique pathway through an RNA intermediate that generates an alternative 5' splice donor site at the point where exon 2 is ligated to exon 1. In the analogous intermediate of human AMPD1, the potential 5' splice donor site created at the boundary of exon 1 and exon 2 was a poor substrate for splicing because of differences in exon 2 sequences, and human AMPD1 was not alternatively spliced. These results demonstrate that in some cases alternative splicing may proceed through an RNA intermediate that generates an alternative splice donor site not present in the primary transcript. Discrimination between alternative 5' splice donor sites in the RNA intermediate of AMPD1 is apparently controlled by tissue-specific and stage-specific signals.

scholarly journals Monoclonal antibodies reveal evolutionary conservation of alternative splicing of the alphaA-crystallin primary transcript

1988 ◽  
Vol 174 (1) ◽  
pp. 133-137 ◽  
Author(s):  
Wiljan HENDRIKS ◽  
Jo SANDERS ◽  
Loe LEIJ ◽  
Frans RAMAEKERS ◽  
Hans BLOEMENDAL ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Alternative Splicing ◽  
Evolutionary Conservation ◽  
Primary Transcript

The ratio of ±KTS splice variants of the Wilms’ tumour suppressor protein WT1 mRNA is determined by an intronic enhancer

2008 ◽  
Vol 86 (4) ◽  
pp. 312-321 ◽  
Author(s):  
Cheng Yang ◽  
Paul J. Romaniuk
Keyword(s):  
Amino Acids ◽  
Alternative Splicing ◽  
Splice Site ◽  
Mutational Analysis ◽  
Tumour Suppressor ◽  
Wilms Tumour ◽  
Mrna Isoforms ◽  
Primary Transcript ◽  
Functional Link ◽  
Intronic Enhancer

Alternative splicing of the primary transcript of the Wilms’ tumour suppressor gene WT1 involving 2 overlapping 5′ splice sites at the end of exon 9 results in the insertion of 2 amino acids (KTS) between zinc fingers 3 and 4 of the protein. The presence or absence of these 3 amino acids has consequences for DNA binding affinity, protein–protein interactions, and subnuclear localization. Disruption of the characteristic +KTS to –KTS ratio of mRNA isoforms as a result of mutations in the +KTS splice site results in Frasier syndrome. Mutational analysis of a WT1 minigene construct was carried out to search for sequences that regulate the ±KTS alternative splicing event. A strong pyrimidine-rich intronic enhancer that increases the use of the +KTS splice site was identified. Cross-linking experiments with nuclear extracts demonstrated that this enhancer specifically binds a protein with a molecular mass of 42 ± 2 kDa. One candidate for this trans-factor is the splicing regulator TIA-1, which binds to the pyrimidine-rich enhancer in the primary transcript from the minigene construct and increases the ±KTS splicing ratio. The observation that TIA-1 and WT1 are both involved in apoptosis supports our proposal for a functional link between these proteins.

scholarly journals Control of calcitonin/calcitonin gene-related peptide pre-mRNA processing by constitutive intron and exon elements.

1993 ◽  
Vol 13 (10) ◽  
pp. 5999-6011 ◽  
Author(s):  
J M Yeakley ◽  
F Hedjran ◽  
J P Morfin ◽  
N Merillat ◽  
M G Rosenfeld ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Calcitonin Gene Related Peptide ◽  
Regulatory Sequences ◽  
Primary Transcript ◽  
Tissue Specific ◽  
Related Peptide ◽  
Thyroid C Cells ◽  
Calcitonin Gene ◽  
Constitutive Splicing ◽  
Specific Regulation

The calcitonin/calcitonin gene-related peptide (CGRP) primary transcript is alternatively spliced in thyroid C cells and neurons, resulting in the tissue-specific production of calcitonin and CGRP mRNAs. Analyses of mutated calcitonin/CGRP transcription units in permanently transfected cell lines have indicated that alternative splicing is regulated by a differential capacity to utilize the calcitonin-specific splice acceptor. The analysis of an extensive series of mutations suggests that tissue-specific regulation of calcitonin mRNA production does not depend on the presence of a single, unique cis-active element but instead appears to be a consequence of suboptimal constitutive splicing signals. While only those mutations that altered constitutive splicing signals affected splice choices, the action of multiple regulatory sequences cannot be formally excluded. Further, we have identified a 13-nucleotide purine-rich element from a constitutive exon that, when placed in exon 4, entirely switches splice site usage in CGRP-producing cells. These data suggest that specific exon recruitment sequences, in combination with other constitutive elements, serve an important function in exon recognition. These results are consistent with the hypothesis that tissue-specific alternative splicing of the calcitonin/CGRP primary transcript is mediated by cell-specific differences in components of the constitutive splicing machinery.

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