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.
Highlights
MULTICELLULAR organisms rely on sophisticated gene expression programs to confer tissue identity and maintain homeostasis
We focused on the general enrichment of C. elegans miRNA families, which have the same “seed” sequence used to target the mRNA (Alvarez-Saavedra and Horvitz 2010), and ranked the enrichment of their targets in genes expressed within each tissue transcriptome
We recently showed that 39untranslated region (39UTR) isoforms generated through alternative polyadenylation (APA) are frequently expressed in a tissue-specific manner in C. elegans intestine, pharynx, and body muscle tissues (Blazie et al 2015)
Summary
MULTICELLULAR organisms rely on sophisticated gene expression programs to confer tissue identity and maintain homeostasis. Several biochemical approaches were used to isolate, map, and study tissue-specific transcriptomes in C. elegans These studies profiled transcriptome changes spanning from large tissues such as intestine (Pauli et al 2006; McGhee et al 2007; Haenni et al 2012), to smaller tissues composed of just a few cells, such as sensory neurons (Takayama et al 2010). Such studies have relied on technologies with limited resolution and less reliable quantification (microarrays or tiling arrays), they have highlighted an unexpected complexity of gene regulatory mechanisms used by cells to maintain their tissue identity and to perform their biological roles. The application of contemporary sequencing technologies to map and study tissue-specific transcriptomes may greatly expand our understanding of the regulatory mechanisms that establish and maintain cellular identity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
