Dissertation
ALTERNATIVE POLYADENYLATION SENSES PHENOTYPIC CHANGES IN TWO ENERGY HOMEOSTASIS MODELS
Doctor of Philosophy (PhD), Washington State University
01/2018
Handle:
https://hdl.handle.net/2376/111233
Abstract
Alternative polyadenylation (APA) sites can be located in either coding sequences or their 3’ untranslated regions (3’UTRs) of genes, thus generating different mRNA isoforms that affect transcriptome diversity and gene expression dynamics and regulate transcript localization, stability, and transport. Energy homeostatic is a very important biological process for an organism’s survival. Adenosine monophosphate-activated protein kinase (AMPK) and the endocannabinoid system are both crucial in maintaining energy homeostasis, however, their underlying mechanisms remain largely unknown. Here we use two energy homeostasis related models, knockout (KO) models (AMPKα1 and AMPKα2 KO mice) and environment treatment model (cannabis plant matter (CPM) exposure rats) to test our hypothesis that altered phenotypic changes seen in these two models are caused by use of alternative polyadenylation sites (APSs). For the first test model, results showed the DE-APSs (differentially expressed APSs) that were related to reduced and increased muscle mass were down-regulated in AMPKα1-KO mice, but up-regulated in AMPKα2-KO mice, respectively. This implies that gene knockout triggers genome plasticity via use of APSs, completing the genome to phenome information transfer processes. For second test model, results indicated that vapor cannabis exposure induced feeding only following a delay, which was accompanied by rapid reduction of hypothalamic alternative polyadenylation usage on mRNAs that regulate glutamatergic synaptic transmission. These two models support our hypothesis and provide new directions for energy homeostasis research filed in future.
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Details
- Title
- ALTERNATIVE POLYADENYLATION SENSES PHENOTYPIC CHANGES IN TWO ENERGY HOMEOSTASIS MODELS
- Creators
- Shuwen Zhang
- Contributors
- Zhihua Jiang (Advisor)Min Du (Committee Member)Meijun Zhu (Committee Member)Jon Davis (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Animal Sciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 113
- Identifiers
- 99900581819901842
- Language
- English
- Resource Type
- Dissertation