The Experts below are selected from a list of 113916 Experts worldwide ranked by ideXlab platform
Kazuhiko Hoshi - One of the best experts on this subject based on the ideXlab platform.
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isoform variant mrnas for sex steroid hormone receptors in humans
Trends in Endocrinology and Metabolism, 2003Co-Authors: Shuji Hirata, Tomoko Shoda, Junzo Kato, Kazuhiko HoshiAbstract:The open reading frames of human sex steroid hormone receptors (hSSHRs) are composed of eight Exons. In addition, the presence of various Exons - including 5'-untranslated Exons, alternative coding Exons and novel 'intronic' Exons - has been demonstrated in the genes encoding hSSHRs. The isoform/variant hSSHR mRNAs generated from thes e Exons can be tentatively classified into seven types. In type 1, different mRNAs are generated with the use of alternative transcription start sites. In type 2, one or more Exons are skipped. In type 3, one or more Exons are duplicated. In type 4, distinct mRNAs containing different 5'-untranslated exon(s) are synthesized. In type 5, distinct mRNAs possessing different coding exon(s) are generated. In type 6, mRNA is synthesized by intronic Exons and coding Exons 4/5-8. In type 7, mRNA with insertion of intronic exon(s) is generated. Here, we review the isoform/variant hSSHR mRNAs and the structure of the genes encoding them.
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novel isoforms of the mrna for human female sex steroid hormone receptors
The Journal of Steroid Biochemistry and Molecular Biology, 2002Co-Authors: Shuji Hirata, Tomoko Shoda, Junzo Kato, Kazuhiko HoshiAbstract:Abstract In our recent reports, the novel isoform cDNAs of the ERα (ERα isoform S cDNA), ERβ (ERβ isoform M cDNA) and PR (PR isoform S and PR isoform T cDNAs) have been identified. These isoform cDNAs contained the previously unidentified 5′-sequences on Exons 4–8 (ERα isoform S cDNA), Exons 5–8 (ERβ isoform M cDNA) or Exons 4–8 (PR isoform S and PR isoform T cDNAs). The genomic DNA analysis revealed that the 5′-sequences were derived from the novel independent Exons, the ERα exon S, ERβ exon M, PR exon S and PR exon T, respectively. Furthermore, the existence of the novel variant mRNA, termed the i45 PR mRNA variant, with the insertion of the previously unidentified Exons, termed the Exons i45a and i45b, has been demonstrated by the reverse transcription-polymerase chain reaction on the RNA of the human uterine endometrium. From these results, we have concluded that the genes for the human female sex steroid hormone receptors contain the novel intronic Exons, that the novel isoform mRNAs are transcribed using the intronic exon and Exons 4–8 (or Exons 5–8) of the gene, and that the novel variant mRNA is generated by the insertion of the intronic Exons in the PR. In the present communication, our recent data along with others on the novel isoform/variant mRNAs for the human female sex steroid hormone receptors will be summarized.
John E Blume - One of the best experts on this subject based on the ideXlab platform.
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discovery of tissue specific Exons using comprehensive human exon microarrays
Genome Biology, 2007Co-Authors: Tyson A Clark, Anthony C Schweitzer, Tina X Chen, Michelle K Staples, Hui Wang, Alan Williams, John E BlumeAbstract:Background Higher eukaryotes express a diverse population of messenger RNAs generated by alternative splicing. Large-scale methods for monitoring gene expression must adapt in order to accurately detect the transcript variation generated by this splicing.
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discovery of tissue specific Exons using comprehensive human exon microarrays
Genome Biology, 2007Co-Authors: Tyson A Clark, Anthony C Schweitzer, Tina X Chen, Michelle K Staples, Hui Wang, Alan Williams, John E BlumeAbstract:Higher eukaryotes express a diverse population of messenger RNAs generated by alternative splicing. Large-scale methods for monitoring gene expression must adapt in order to accurately detect the transcript variation generated by this splicing. We have designed a high-density oligonucleotide microarray with probesets for more than one million annotated and predicted Exons in the human genome. Using these arrays and a simple algorithm that normalizes exon signal to signal from the gene as a whole, we have identified tissue-specific Exons from a panel of 16 different normal adult tissues. RT-PCR validation confirms approximately 86% of the predicted tissue-enriched probesets. Pair-wise comparisons between the tissues suggest that as many as 73% of detected genes are differentially alternatively spliced. We also demonstrate how an inclusive exon microarray can be used to discover novel alternative splicing events. As examples, 17 new tissue-specific Exons from 11 genes were validated by RT-PCR and sequencing. In conjunction with a conceptually simple algorithm, comprehensive exon microarrays can detect tissue-specific alternative splicing events. Our data suggest significant expression outside of known Exons and well annotated genes and a high frequency of alternative splicing events. In addition, we identified and validated a number of novel Exons with tissue-specific splicing patterns. The tissue map data will likely serve as a valuable source of information on the regulation of alternative splicing.
Shuji Hirata - One of the best experts on this subject based on the ideXlab platform.
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isoform variant mrnas for sex steroid hormone receptors in humans
Trends in Endocrinology and Metabolism, 2003Co-Authors: Shuji Hirata, Tomoko Shoda, Junzo Kato, Kazuhiko HoshiAbstract:The open reading frames of human sex steroid hormone receptors (hSSHRs) are composed of eight Exons. In addition, the presence of various Exons - including 5'-untranslated Exons, alternative coding Exons and novel 'intronic' Exons - has been demonstrated in the genes encoding hSSHRs. The isoform/variant hSSHR mRNAs generated from thes e Exons can be tentatively classified into seven types. In type 1, different mRNAs are generated with the use of alternative transcription start sites. In type 2, one or more Exons are skipped. In type 3, one or more Exons are duplicated. In type 4, distinct mRNAs containing different 5'-untranslated exon(s) are synthesized. In type 5, distinct mRNAs possessing different coding exon(s) are generated. In type 6, mRNA is synthesized by intronic Exons and coding Exons 4/5-8. In type 7, mRNA with insertion of intronic exon(s) is generated. Here, we review the isoform/variant hSSHR mRNAs and the structure of the genes encoding them.
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novel isoforms of the mrna for human female sex steroid hormone receptors
The Journal of Steroid Biochemistry and Molecular Biology, 2002Co-Authors: Shuji Hirata, Tomoko Shoda, Junzo Kato, Kazuhiko HoshiAbstract:Abstract In our recent reports, the novel isoform cDNAs of the ERα (ERα isoform S cDNA), ERβ (ERβ isoform M cDNA) and PR (PR isoform S and PR isoform T cDNAs) have been identified. These isoform cDNAs contained the previously unidentified 5′-sequences on Exons 4–8 (ERα isoform S cDNA), Exons 5–8 (ERβ isoform M cDNA) or Exons 4–8 (PR isoform S and PR isoform T cDNAs). The genomic DNA analysis revealed that the 5′-sequences were derived from the novel independent Exons, the ERα exon S, ERβ exon M, PR exon S and PR exon T, respectively. Furthermore, the existence of the novel variant mRNA, termed the i45 PR mRNA variant, with the insertion of the previously unidentified Exons, termed the Exons i45a and i45b, has been demonstrated by the reverse transcription-polymerase chain reaction on the RNA of the human uterine endometrium. From these results, we have concluded that the genes for the human female sex steroid hormone receptors contain the novel intronic Exons, that the novel isoform mRNAs are transcribed using the intronic exon and Exons 4–8 (or Exons 5–8) of the gene, and that the novel variant mRNA is generated by the insertion of the intronic Exons in the PR. In the present communication, our recent data along with others on the novel isoform/variant mRNAs for the human female sex steroid hormone receptors will be summarized.
Christopher Lee - One of the best experts on this subject based on the ideXlab platform.
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protein modularity of alternatively spliced Exons is associated with tissue specific regulation of alternative splicing
PLOS Genetics, 2005Co-Authors: Yi Xing, Christopher LeeAbstract:Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of “modular” Exons that can be inserted or removed from the transcripts without affecting the rest of the protein. To understand the precise roles of these modular Exons, in this paper we have analyzed microarray data for 3,126 alternatively spliced Exons across ten mouse tissues generated by Pan and coworkers. We show that modular Exons are strongly associated with tissue-specific regulation of alternative splicing. Exons that are alternatively spliced at uniformly high transcript inclusion levels or uniformly low levels show no preference for protein modularity. In contrast, alternatively spliced Exons with dramatic changes of inclusion levels across mouse tissues (referred to as “tissue-switched” Exons) are both strikingly biased to be modular and are strongly conserved between human and mouse. The analysis of different subsets of tissue-switched Exons shows that the increased protein modularity cannot be explained by the overall exon inclusion level, but is specifically associated with tissue-switched alternative splicing.
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evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation
Nucleic Acids Research, 2004Co-Authors: Alissa Resch, Yi Xing, Alexander V Alekseyenko, Barmak Modrek, Christopher LeeAbstract:Recently there has been much interest in assessing the role of alternative splicing in evolution. We have sought to measure functional selection pressure on alternatively spliced single-exon skips, by calculating the fraction that are an exact multiple of 3 nt in length and therefore preserve protein reading-frame in both the exon-inclusion and exon-skip splice forms. The frame-preservation ratio (defined as the number of Exons that are an exact multiple of three in length, divided by the number of Exons that are not) was slightly above random for both constitutive Exons and alternatively spliced Exons as a whole in human and mouse. However, orthologous Exons that were observed to be alternatively spliced in the expressed sequence tag data from two or more organisms showed a substantially increased bias to be frame-preserving. This effect held true only for Exons within the protein coding region, and not the untranslated region. In five animal genomes (human, mouse, rat, zebrafish, Drosophila), we observed an association between these conserved alternative splicing events and increased selection pressure for frame-preservation. Surprisingly, this effect became stronger as a function of decreasing exon inclusion level: for alternatively spliced Exons that were included in a majority of the gene's transcripts, the frame-preservation bias was no higher than that of constitutive Exons, whereas for alternatively spliced Exons that were included in only a minority of the gene's transcripts, the frame-preservation bias increased nearly 20-fold. These data indicate that a subpopulation of modern alternative splicing events was present in the common ancestors of these genomes, and was under functional selection pressure to preserve the protein reading frame.
Yi Xing - One of the best experts on this subject based on the ideXlab platform.
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widespread establishment and regulatory impact of alu Exons in human genes
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Shihao Shen, Lan Lin, James J Cai, Peng Jiang, Elizabeth J Kenkel, Mallory R Stroik, Seiko Sato, Beverly L Davidson, Yi XingAbstract:The Alu element has been a major source of new Exons during primate evolution. Thousands of human genes contain spliced Exons derived from Alu elements. However, identifying Alu Exons that have acquired genuine biological functions remains a major challenge. We investigated the creation and establishment of Alu Exons in human genes, using transcriptome profiles of human tissues generated by high-throughput RNA sequencing (RNA-Seq) combined with extensive RT-PCR analysis. More than 25% of Alu Exons analyzed by RNA-Seq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu Exons in human genes. Genes encoding zinc finger transcription factors have significantly higher levels of Alu exonization. Importantly, Alu Exons with high splicing activities are strongly enriched in the 5′-UTR, and two-thirds (10/15) of 5′-UTR Alu Exons tested by luciferase reporter assays significantly alter mRNA translational efficiency. Mutational analysis reveals the specific molecular mechanisms by which newly created 5′-UTR Alu Exons modulate translational efficiency, such as the creation or elongation of upstream ORFs that repress the translation of the primary ORFs. This study presents genomic evidence that a major functional consequence of Alu exonization is the lineage-specific evolution of translational regulation. Moreover, the preferential creation and establishment of Alu Exons in zinc finger genes suggest that Alu exonization may have globally affected the evolution of primate and human transcriptomes by regulating the protein production of master transcriptional regulators in specific lineages.
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protein modularity of alternatively spliced Exons is associated with tissue specific regulation of alternative splicing
PLOS Genetics, 2005Co-Authors: Yi Xing, Christopher LeeAbstract:Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of “modular” Exons that can be inserted or removed from the transcripts without affecting the rest of the protein. To understand the precise roles of these modular Exons, in this paper we have analyzed microarray data for 3,126 alternatively spliced Exons across ten mouse tissues generated by Pan and coworkers. We show that modular Exons are strongly associated with tissue-specific regulation of alternative splicing. Exons that are alternatively spliced at uniformly high transcript inclusion levels or uniformly low levels show no preference for protein modularity. In contrast, alternatively spliced Exons with dramatic changes of inclusion levels across mouse tissues (referred to as “tissue-switched” Exons) are both strikingly biased to be modular and are strongly conserved between human and mouse. The analysis of different subsets of tissue-switched Exons shows that the increased protein modularity cannot be explained by the overall exon inclusion level, but is specifically associated with tissue-switched alternative splicing.
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evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation
Nucleic Acids Research, 2004Co-Authors: Alissa Resch, Yi Xing, Alexander V Alekseyenko, Barmak Modrek, Christopher LeeAbstract:Recently there has been much interest in assessing the role of alternative splicing in evolution. We have sought to measure functional selection pressure on alternatively spliced single-exon skips, by calculating the fraction that are an exact multiple of 3 nt in length and therefore preserve protein reading-frame in both the exon-inclusion and exon-skip splice forms. The frame-preservation ratio (defined as the number of Exons that are an exact multiple of three in length, divided by the number of Exons that are not) was slightly above random for both constitutive Exons and alternatively spliced Exons as a whole in human and mouse. However, orthologous Exons that were observed to be alternatively spliced in the expressed sequence tag data from two or more organisms showed a substantially increased bias to be frame-preserving. This effect held true only for Exons within the protein coding region, and not the untranslated region. In five animal genomes (human, mouse, rat, zebrafish, Drosophila), we observed an association between these conserved alternative splicing events and increased selection pressure for frame-preservation. Surprisingly, this effect became stronger as a function of decreasing exon inclusion level: for alternatively spliced Exons that were included in a majority of the gene's transcripts, the frame-preservation bias was no higher than that of constitutive Exons, whereas for alternatively spliced Exons that were included in only a minority of the gene's transcripts, the frame-preservation bias increased nearly 20-fold. These data indicate that a subpopulation of modern alternative splicing events was present in the common ancestors of these genomes, and was under functional selection pressure to preserve the protein reading frame.
