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Genetics. 2017 Jun;206(2):757-774. doi: 10.1534/genetics.116.196774. Epub 2017 Mar 27.

Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues.

Author information

1
Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, Arizona 85281.
2
Virginia G. Piper Center for Personalized Diagnostics, The Biodesign Institute at Arizona State University, Tempe, Arizona 85281.
3
Barrett Honors College, Arizona State University, Tempe, Arizona 85281.
4
College of Letters and Sciences, Interdisciplinary Studies, Biological Sciences and Informatics, Arizona State University, Tempe, Arizona 85281.
5
Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, Arizona 85281 mangone@asu.edu.

Abstract

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.

KEYWORDS:

C. elegans; alternative polyadenylation; miRNA; transcriptome

PMID:
28348061
PMCID:
PMC5499184
DOI:
10.1534/genetics.116.196774
[Indexed for MEDLINE]
Free PMC Article

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