Poster abstracts
Poster number 71 submitted by Zeqing Jiang
The Role of 5’ UTR in gene expression regulation
Zeqing Jiang (Department of Biological Sciences, Carnegie Mellon University), Gemma May (Department of Biological Sciences, Carnegie Mellon University), Cassia Williams-Rogers (Washington University in St. Louis), Haoran Wang (Department of Biological Sciences, Carnegie Mellon University), Dr. Joel Mcmanus (Department of Biological Sciences, Carnegie Mellon University)
Abstract:
Protein synthesis is a vital process in all living organisms. Titin (TTN), the largest protein found in the human body, serves a critical function in muscle contraction and the operation of sarcomeres. The mutation in the titin protein can cause the development of typical cardiac diseases like dilated cardiomyopathy and heart failure. Notably, the Titin 5’ UTR is among the most conserved in humans. We performed DMS-Map to model the structure of the Titin 5’ UTR. This revealed three RNA stem loops, which are also conserved. The 5’ UTR also harbors a tandem upstream open reading frame (uORF). We used luciferase reporter assays to evaluate the influence of these stem loops and uORFs on titin gene expression. Our results shows that disruption of the stem-loop structures and uORFs increased reporter expression in both HEK293T cells and C2C12 myoblast cells. Interestingly, Titin stemloop 2 has been lost in two clades of South American bats and rodents. However, the Titin UTRs from two of these species appear to repress translation as well as the human 5’ UTR. This work suggests that highly conserved sequences in the Titin 5’ UTR collectively reduce ribosome loading, which may be beneficial for Titin expression in heart and skeletal muscle tissue.
References:
1. Shadrin, I Y et al. (2016). Striated muscle function, regeneration, and repair. Cellular and molecular life sciences: CMLS vol. 73,22: 4175-4202.
Keywords: Titin, 5 UTR, RNA secondary structure