Alternative isoform regulation in human tissue transcriptomes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-11-27

AUTHORS

Eric T. Wang, Rickard Sandberg, Shujun Luo, Irina Khrebtukova, Lu Zhang, Christine Mayr, Stephen F. Kingsmore, Gary P. Schroth, Christopher B. Burge

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. More... »

PAGES

470-476

References to SciGraph publications

  • 2001-02-15. Initial sequencing and analysis of the human genome in NATURE
  • 2004-09-28. Strengths and weaknesses of EST-based prediction of tissue-specific alternative splicing in BMC GENOMICS
  • 2002-04-04. An extensive network of coupling among gene expression machines in NATURE
  • 2005-07-24. Target RNA motif and target mRNAs of the Quaking STAR protein in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2008-01-13. Genome-wide analysis of transcript isoform variation in humans in NATURE GENETICS
  • 2005-02-27. Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals in NATURE
  • 2008-05-30. Mapping and quantifying mammalian transcriptomes by RNA-Seq in NATURE METHODS
  • 2007-06-07. Spatial preferences of microRNA targets in 3' untranslated regions in BMC GENOMICS
  • 2006-09-01. The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements in NATURE BIOTECHNOLOGY
  • 2005-05-01. Understanding alternative splicing: towards a cellular code in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2002-10-23. Finding signals that regulate alternative splicing in the post-genomic era in GENOME BIOLOGY
  • 2004-09-13. Variation in alternative splicing across human tissues in GENOME BIOLOGY
  • 2008-11-02. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing in NATURE GENETICS
  • 2006-11-01. An RNA map predicting Nova-dependent splicing regulation in NATURE
  • 2008-11-02. HITS-CLIP yields genome-wide insights into brain alternative RNA processing in NATURE
  • Journal

    TITLE

    Nature

    ISSUE

    7221

    VOLUME

    456

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature07509

    DOI

    http://dx.doi.org/10.1038/nature07509

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1029002744

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18978772


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