Alternative polyadenylation directs tissue-specific miRNA targeting in Caenorhabditis elegans somatic tissues

Stephen M. Blazie, Heather C. Geissel, Henry Wilky, Rajan Joshi, Jason Newbern, Marco Mangone

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)757-774
Number of pages18
JournalGenetics
Volume206
Issue number2
DOIs
StatePublished - Jun 1 2017

Fingerprint

Polyadenylation
Caenorhabditis elegans
MicroRNAs
Genes
Muscles
Messenger RNA
Protein Isoforms
Caenorhabditis elegans Proteins
GABAergic Neurons
N-Methylaspartate
Pharynx
Transcriptome
Intestines
Proteins

Keywords

  • Alternative polyadenylation
  • C. elegans
  • miRNA
  • Transcriptome

ASJC Scopus subject areas

  • Genetics

Cite this

Alternative polyadenylation directs tissue-specific miRNA targeting in Caenorhabditis elegans somatic tissues. / Blazie, Stephen M.; Geissel, Heather C.; Wilky, Henry; Joshi, Rajan; Newbern, Jason; Mangone, Marco.

In: Genetics, Vol. 206, No. 2, 01.06.2017, p. 757-774.

Research output: Contribution to journalArticle

Blazie, Stephen M. ; Geissel, Heather C. ; Wilky, Henry ; Joshi, Rajan ; Newbern, Jason ; Mangone, Marco. / Alternative polyadenylation directs tissue-specific miRNA targeting in Caenorhabditis elegans somatic tissues. In: Genetics. 2017 ; Vol. 206, No. 2. pp. 757-774.
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