Translational regulation of HtrA2 during brown fat differentiation

• Main Author: Chang, Zhi Wei
• Other Authors: Guo Huili
• Format: Final Year Project
• Language: English
• Published: 2019
• Subjects: DRNTU::Science::Biological sciences
• Online Access: http://hdl.handle.net/10356/77354
• Institution: Nanyang Technological University

Brown fat is well known for its adaptive thermoregulatory functions attributed to its abundant mitochondria containing a unique uncoupling protein, UCP-1, which converts excess energy into heat. With its potential in mitigating obesity and metabolic diseases, brown fat has increasingly garnered research attention. While much of transcriptional regulation has been elucidated, translational regulation of brown adipocyte differentiation remains elusive. In our study, we identified and validated HtrA2 as a translationally regulated gene during brown fat differentiation, by comparing quantitative RT-PCR with preliminary RNA-seq results. HtrA2 demonstrates a notable increase in translational efficiency despite a significant reduction in mRNA abundance during brown fat differentiation. This finding suggests that an unknown compensatory mechanism could be involved during translation. Hence, in our study, we are interested in identifying RBPs bound to HtrA2 mRNA which may regulate its translational efficiency, through the use of MS2-TRAP. We also attempted to determine the role of HtrA2 protein in mitochondrial biogenesis and brown adipogenesis by inhibiting HtrA2 translation using morpholino oligonucleotide. The understanding of translational regulation in brown fat could reveal beneficial insights, facilitating its use for our therapeutic advantage to tackle obesity and its related diseases in the near future.