integrative analysis of alternative polyadenylation and microRNA regulation in Caenorhabditis elegansAn
Recent transcriptome data from yeast, worm, plants, and humans has shown that alternative polyadenylation (APA), a mechanism that enables expression of multiple 3′UTR isoforms for the same gene, is widespread in eukaryotic organisms. It is still poorly understood why metazoans require multiple 3′UTRs for the same gene, but accumulating evidence suggests that APA is largely regulated at a tissue-specific level. APA may direct combinatorial variation between cis-elements and microRNAs, perhaps to regulate gene expression in a tissue-specific manner. Apart from a few single gene anecdotes, this idea has not been systematically explored.
This dissertation research employs a systems biology approach to study the somatic tissue dynamics of APA and its impact on microRNA targeting networks in the small nematode C. elegans. In the first aim, tools were developed and applied to isolate and sequence mRNA from worm intestine and muscle tissues, which revealed pervasive tissue-specific APA correlated with microRNA regulation. The second aim provides genetic evidence that two worm genes use APA to escape repression by microRNAs in the body muscle. Finally, in aim three, mRNA from five additional somatic worm tissues was sequenced and their 3′ends mapped, allowing for an integrative study of APA and microRNA targeting dynamics in worms. Together, this work provides evidence that APA is a pervasive mechanism operating in somatic tissues of C. elegans with the potential to significantly rearrange their microRNA regulatory networks and precisely dose their gene expression.]]>autBlazie, Stephen MthsMangone, MarcodgcLaBaer, JoshdgcLake, DougdgcNewfeld, StuartpblArizona State UniversityengPartial requirement for: Ph.D., Arizona State University, 2016Includes bibliographical references (pages 174-191)Field of study: Molecular and Cellular Biologyby Stephen M. Blaziehttps://hdl.handle.net/2286/R.I.3848300Doctoral DissertationAcademic thesesxiii, 191 pages : illustrations (some color)114647869551630347858154421adminIn CopyrightAll Rights Reserved2016TextMolecular BiologyGeneticsGene ExpressionRNACaenorhabditis elegans--Genetics.Caenorhabditis elegans