Alternative isoform regulation in human tissue transcriptomes.
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| Title: | Alternative isoform regulation in human tissue transcriptomes. |
|---|---|
| Authors: | Wang, Eric T., Sandberg, Rickard, Luo, Shujun, Khrebtukova, Irina, Zhang, Lu, Mayr, Christine, Kingsmore, Stephen F., Schroth, Gary P., Burge, Christopher B. |
| Source: | Nature. 11/27/2008, Vol. 456 Issue 7221, p470-476. 7p. 1 Diagram, 1 Chart, 3 Graphs. |
| Subjects: | Messenger RNA, Genetic polymorphisms, Cell lines, Tissue extracts, Nucleotide sequence, Gene mapping, RNA splicing, Scission (Chemistry) |
| Abstract: | Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon–exon junctions indicated that 92–94% of human genes undergo alternative splicing, ∼86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or ‘switch-like’ regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3′ untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 35483673 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Alternative isoform regulation in human tissue transcriptomes. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Wang%2C+Eric+T%2E%22">Wang, Eric T.</searchLink><br /><searchLink fieldCode="AR" term="%22Sandberg%2C+Rickard%22">Sandberg, Rickard</searchLink><br /><searchLink fieldCode="AR" term="%22Luo%2C+Shujun%22">Luo, Shujun</searchLink><br /><searchLink fieldCode="AR" term="%22Khrebtukova%2C+Irina%22">Khrebtukova, Irina</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Lu%22">Zhang, Lu</searchLink><br /><searchLink fieldCode="AR" term="%22Mayr%2C+Christine%22">Mayr, Christine</searchLink><br /><searchLink fieldCode="AR" term="%22Kingsmore%2C+Stephen+F%2E%22">Kingsmore, Stephen F.</searchLink><br /><searchLink fieldCode="AR" term="%22Schroth%2C+Gary+P%2E%22">Schroth, Gary P.</searchLink><br /><searchLink fieldCode="AR" term="%22Burge%2C+Christopher+B%2E%22">Burge, Christopher B.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 11/27/2008, Vol. 456 Issue 7221, p470-476. 7p. 1 Diagram, 1 Chart, 3 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+lines%22">Cell lines</searchLink><br /><searchLink fieldCode="DE" term="%22Tissue+extracts%22">Tissue extracts</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotide+sequence%22">Nucleotide sequence</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+mapping%22">Gene mapping</searchLink><br /><searchLink fieldCode="DE" term="%22RNA+splicing%22">RNA splicing</searchLink><br /><searchLink fieldCode="DE" term="%22Scission+%28Chemistry%29%22">Scission (Chemistry)</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon–exon junctions indicated that 92–94% of human genes undergo alternative splicing, ∼86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or ‘switch-like’ regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3′ untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/nature07509 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 470 Subjects: – SubjectFull: Messenger RNA Type: general – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Cell lines Type: general – SubjectFull: Tissue extracts Type: general – SubjectFull: Nucleotide sequence Type: general – SubjectFull: Gene mapping Type: general – SubjectFull: RNA splicing Type: general – SubjectFull: Scission (Chemistry) Type: general Titles: – TitleFull: Alternative isoform regulation in human tissue transcriptomes. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Wang, Eric T. – PersonEntity: Name: NameFull: Sandberg, Rickard – PersonEntity: Name: NameFull: Luo, Shujun – PersonEntity: Name: NameFull: Khrebtukova, Irina – PersonEntity: Name: NameFull: Zhang, Lu – PersonEntity: Name: NameFull: Mayr, Christine – PersonEntity: Name: NameFull: Kingsmore, Stephen F. – PersonEntity: Name: NameFull: Schroth, Gary P. – PersonEntity: Name: NameFull: Burge, Christopher B. IsPartOfRelationships: – BibEntity: Dates: – D: 27 M: 11 Text: 11/27/2008 Type: published Y: 2008 Identifiers: – Type: issn-print Value: 00280836 Numbering: – Type: volume Value: 456 – Type: issue Value: 7221 Titles: – TitleFull: Nature Type: main |
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