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mRNA expression dynamics promote and maintain the identity of somatic tissues in living organisms; however, their impact in post-transcriptional gene regulation in these processes is not fully understood. Here, we applied the PAT-Seq approach to systematically isolate, sequence, and ma

mRNA expression dynamics promote and maintain the identity of somatic tissues in living organisms; however, their impact in post-transcriptional gene regulation in these processes is not fully understood. Here, we applied the PAT-Seq approach to systematically isolate, sequence, and map tissue-specific mRNA from five highly studied Caenorhabditis elegans somatic tissues: GABAergic and NMDA neurons, arcade and intestinal valve cells, seam cells, and hypodermal tissues, and studied their mRNA expression dynamics. The integration of these datasets with previously profiled transcriptomes of intestine, pharynx, and body muscle tissues, precisely assigns tissue-specific expression dynamics for 60% of all annotated C. elegans protein-coding genes, providing an important resource for the scientific community. The mapping of 15,956 unique high-quality tissue-specific polyA sites in all eight somatic tissues reveals extensive tissue-specific 3′untranslated region (3′UTR) isoform switching through alternative polyadenylation (APA) . Almost all ubiquitously transcribed genes use APA and harbor miRNA targets in their 3′UTRs, which are commonly lost in a tissue-specific manner, suggesting widespread usage of post-transcriptional gene regulation modulated through APA to fine tune tissue-specific protein expression. Within this pool, the human disease gene C. elegans orthologs rack-1 and tct-1 use APA to switch to shorter 3′UTR isoforms in order to evade miRNA regulation in the body muscle tissue, resulting in increased protein expression needed for proper body muscle function. Our results highlight a major positive regulatory role for APA, allowing genes to counteract miRNA regulation on a tissue-specific basis.

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    Title
    • Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis Elegans Somatic Tissues
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    Date Created
    2017-03-27
    Resource Type
  • Text
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    Identifier
    • Digital object identifier: 10.1534/genetics.116.196774
    • Identifier Type
      International standard serial number
      Identifier Value
      0016-6731
    • Identifier Type
      International standard serial number
      Identifier Value
      1943-2631
    Note
    • The final version of this article, as published in Genetics, can be viewed online at: http://www.genetics.org/content/206/2/757

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    Blazie, S. M., Geissel, H. C., Wilky, H., Joshi, R., Newbern, J., & Mangone, M. (2017). Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues. Genetics, 206(2), 757-774. doi:10.1534/genetics.116.196774

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