scholarly journals A 3′ splice site consensus sequence mutation in the intron 3 of the α-galactosidase a gene in a patient with Fabry disease

1991 ◽  
Vol 36 (3) ◽  
pp. 245-250 ◽  
Author(s):  
Tohru Yokoi ◽  
Kazuko Shinoda ◽  
Ichiro Ohno ◽  
Kimitaka Kato ◽  
Toshio Miyawaki ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Splice Site ◽  
Consensus Sequence ◽  
Site Consensus

Role of the 3′ splice site consensus sequence in mammalian pre-mRNA splicing

Nature ◽  
1985 ◽  
Vol 317 (6039) ◽  
pp. 732-734 ◽  
Author(s):  
Barbara Ruskin ◽  
Michael R. Green
Keyword(s):  
Splice Site ◽  
Consensus Sequence ◽  
Mrna Splicing ◽  
Site Consensus

scholarly journals Molecular Characterization of PK-LR Gene in Pyruvate Kinase–Deficient Italian Patients

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3847-3852 ◽  
Author(s):  
Alberto Zanella ◽  
Paola Bianchi ◽  
Luciano Baronciani ◽  
Manuela Zappa ◽  
Elena Bredi ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Splice Site ◽  
Stop Codon ◽  
Consensus Sequence ◽  
Missense Mutations ◽  
Frequent Mutation ◽  
Unstable Gene ◽  
Site Consensus ◽  
Conserved Amino Acids

We studied the PK-LR gene in 15 unrelated Italian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase (PK) deficiency. Fourteen different mutations were detected among 26 mutated alleles identified: a five-nucleotide (nt) deletion (227 to 231), two splice-site (1269C and IVS3(−2)c), 10 missense (514C, 787T, 823A, 993A, 994A, 1168A, 1456T, 1529A, 1552A, and 1594T) and one nonsense mutation(s) (721T). Eight of these (deletion 227-231, 1269C, IVS3(−2)c, 514C, 787T, 823A, 1168A, and 1552A) were novel. Moreover, a new polymorphic site was detected in the 3′ untranslated region of the mRNA (C/T, nucleotide 1738). The deletion 227-231 causes a stop codon after amino acid 77, probably resulting in an unstable gene product. Mutations 1269C and IVS3(−2)c lead to an alteration of the 5′ and 3′ splice-site consensus sequence, respectively; cDNA analysis failed to reveal any abnormal transcript, suggesting that these mutations generate an unstable mRNA that is rapidly degraded. Of the five new missense mutations, 823A (Gly275-Arg) and 1168A (Asp390-Asn) involve highly conserved amino acids, 514C (Glu172-Gln) and 1552A (Arg518-Ser), although found in less conserved regions, affect the balance of the electric charges of the protein. Mutation 787T (Gly263-Trp) is likely to determine strong modifications in the local structure of the molecule. The most frequent mutation in Italy appears to be 1456T (seven of 30 alleles), followed by 1529A (three of 30) and 994A (three of 30). A correlation was found between mutations, biochemical characteristics of the enzyme, and clinical course of the disease.

scholarly journals Molecular Characterization of PK-LR Gene in Pyruvate Kinase–Deficient Italian Patients

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3847-3852 ◽  
Author(s):  
Alberto Zanella ◽  
Paola Bianchi ◽  
Luciano Baronciani ◽  
Manuela Zappa ◽  
Elena Bredi ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Splice Site ◽  
Stop Codon ◽  
Consensus Sequence ◽  
Missense Mutations ◽  
Frequent Mutation ◽  
Unstable Gene ◽  
Site Consensus ◽  
Conserved Amino Acids

Abstract We studied the PK-LR gene in 15 unrelated Italian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase (PK) deficiency. Fourteen different mutations were detected among 26 mutated alleles identified: a five-nucleotide (nt) deletion (227 to 231), two splice-site (1269C and IVS3(−2)c), 10 missense (514C, 787T, 823A, 993A, 994A, 1168A, 1456T, 1529A, 1552A, and 1594T) and one nonsense mutation(s) (721T). Eight of these (deletion 227-231, 1269C, IVS3(−2)c, 514C, 787T, 823A, 1168A, and 1552A) were novel. Moreover, a new polymorphic site was detected in the 3′ untranslated region of the mRNA (C/T, nucleotide 1738). The deletion 227-231 causes a stop codon after amino acid 77, probably resulting in an unstable gene product. Mutations 1269C and IVS3(−2)c lead to an alteration of the 5′ and 3′ splice-site consensus sequence, respectively; cDNA analysis failed to reveal any abnormal transcript, suggesting that these mutations generate an unstable mRNA that is rapidly degraded. Of the five new missense mutations, 823A (Gly275-Arg) and 1168A (Asp390-Asn) involve highly conserved amino acids, 514C (Glu172-Gln) and 1552A (Arg518-Ser), although found in less conserved regions, affect the balance of the electric charges of the protein. Mutation 787T (Gly263-Trp) is likely to determine strong modifications in the local structure of the molecule. The most frequent mutation in Italy appears to be 1456T (seven of 30 alleles), followed by 1529A (three of 30) and 994A (three of 30). A correlation was found between mutations, biochemical characteristics of the enzyme, and clinical course of the disease.

scholarly journals Genes of nuclear encoded mitochondrial proteins: evidence for a variant of the 3′ splice-site consensus sequence

1987 ◽  
Vol 15 (24) ◽  
pp. 10083-10086 ◽  
Author(s):  
Nenad Juretić ◽  
Rolf Jausso ◽  
Urs Mattes ◽  
Philipp Christen
Keyword(s):  
Splice Site ◽  
Consensus Sequence ◽  
Mitochondrial Proteins ◽  
Site Consensus

A 3′ splice site consensus sequence mutation in the cystic fibrosis gene

1990 ◽  
Vol 85 (4) ◽  
pp. 450-453 ◽  
Author(s):  
H. Guillermit ◽  
P. Fanent ◽  
C. Ferec
Keyword(s):  
Cystic Fibrosis ◽  
Splice Site ◽  
Consensus Sequence ◽  
Cystic Fibrosis Gene ◽  
Site Consensus

CHARACTERIZATION OF THE SPLICE SITES IN GT–AG AND GC–AG INTRONS IN HIGHER EUKARYOTES USING FULL-LENGTH cDNAs

2004 ◽  
Vol 02 (02) ◽  
pp. 309-331 ◽  
Author(s):  
SUMIE KITAMURA–ABE ◽  
HITOMI ITOH ◽  
TAKANORI WASHIO ◽  
AKIHIRO TSUTSUMI ◽  
MASARU TOMITA
Keyword(s):  
Alternative Splice ◽  
Splice Site ◽  
Consensus Sequence ◽  
Full Length ◽  
Splice Sites ◽  
Consensus Sequences ◽  
Full Length Cdna ◽  
Strong Consensus ◽  
Higher Eukaryotes

For the purpose of analyzing the relation between the splice sites and the order of introns, we conducted the following analysis for the GT–AG and GC–AG splice site groups. First, the pre-mRNAs of H. sapiens, M. musculus, D. melanogaster, A. thaliana and O. sativa were sampled by mapping the full-length cDNA to the genomes. Next, the consensus sequences at different regions of pre-mRNAs were analyzed in the five species. We also investigated the mononucleotide and dinucleotide frequencies in the extensive regions around the 5' splice sites (5'ss) and 3' splice sites (3'ss). As a result, differential frequencies of nucleotides at the first 5'ss in both the GT–AG and GC–AG splice site groups were observed in A. thaliana and O. sativa pre-mRNAs. The trend, which indicates that GC 5'ss possess strong consensus sequences, was observed not only in mammalian pre-mRNAs but also in the pre-mRNAs of D. melanogaster, A. thaliana and O. sativa. Furthermore, we examined the consensus sequences of the constitutive and alternative splice sites. It was suggested that in the case of the alternative GC–AG introns, the tendency to have a weak consensus sequence at 5'ss is different between H. sapiens and M. musculus pre-mRNAs.

scholarly journals RNA Splicing at Human Immunodeficiency Virus Type 1 3′ Splice Site A2 Is Regulated by Binding of hnRNP A/B Proteins to an Exonic Splicing Silencer Element

2001 ◽  
Vol 75 (18) ◽  
pp. 8487-8497 ◽  
Author(s):  
Patricia S. Bilodeau ◽  
Jeffrey K. Domsic ◽  
Akila Mayeda ◽  
Adrian R. Krainer ◽  
C. Martin Stoltzfus
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Splice Site ◽  
Rna Splicing ◽  
Consensus Sequence ◽  
Mrna Levels ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

ABSTRACT The synthesis of human immunodeficiency virus type 1 (HIV-1) mRNAs is a complex process by which more than 30 different mRNA species are produced by alternative splicing of a single primary RNA transcript. HIV-1 splice sites are used with significantly different efficiencies, resulting in different levels of mRNA species in infected cells. Splicing of Tat mRNA, which is present at relatively low levels in infected cells, is repressed by the presence of exonic splicing silencers (ESS) within the two tat coding exons (ESS2 and ESS3). These ESS elements contain the consensus sequence PyUAG. Here we show that the efficiency of splicing at 3′ splice site A2, which is used to generate Vpr mRNA, is also regulated by the presence of an ESS (ESSV), which has sequence homology to ESS2 and ESS3. Mutagenesis of the three PyUAG motifs within ESSV increases splicing at splice site A2, resulting in increased Vpr mRNA levels and reduced skipping of the noncoding exon flanked by A2 and D3. The increase in Vpr mRNA levels and the reduced skipping also occur when splice site D3 is mutated toward the consensus sequence. By in vitro splicing assays, we show that ESSV represses splicing when placed downstream of a heterologous splice site. A1, A1B, A2, and B1 hnRNPs preferentially bind to ESSV RNA compared to ESSV mutant RNA. Each of these proteins, when added back to HeLa cell nuclear extracts depleted of ESSV-binding factors, is able to restore splicing repression. The results suggest that coordinate repression of HIV-1 RNA splicing is mediated by members of the hnRNP A/B protein family.

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