Seminars

Post-transcriptional code of gene regulation:

The biological significance of RNA binding protein in health and disease

Eun Kyung Lee, Ph.D.

Department of Biochemistry, College of Medicine, The Catholic University of Korea

Timely and precise regulation of gene expression is crucial for maintaining homeostasis in living organisms, as aberrant gene expression can lead to impaired cellular functions and contribute to the development of various diseases. Our lab focuses on elucidating the molecular mechanisms governing gene expression at the RNA level, particularly through post-transcriptional processes involving RNA-binding proteins and non-coding RNAs. In this presentation, we will overview the regulatory mechanisms of RNA metabolism and share our findings on the significance of RNA-binding proteins in particular, cellular senescence.

Senescent cells exhibit diverse changes in morphology, proliferative capacity, senescence-associated secretory phenotype (SASP) production, and mitochondrial homeostasis, often displaying elongated mitochondria—a hallmark of cellular senescence. However, the regulatory mechanisms underlying this phenomenon remain largely unexplored. Our study provides evidence of decreased levels of TIA-1, a key regulator of mitochondrial dynamics, in both replicative and ionizing radiation (IR)-induced senescence models. The downregulation of TIA-1 triggers mitochondrial elongation and enhances the expression of senescence-associated β-galactosidase, a marker of cellular senescence, in human foreskin fibroblast HS27 cells and human keratinocyte HaCaT cells. Conversely, overexpression of TIA-1 mitigates IR-induced cellular senescence. We also identified the miR-30-5p family as a novel regulator of TIA-1 expression, with increased expression of this family driving mitochondrial elongation and promoting cellular senescence in response to IR. Collectively, our findings underscore the significance of the miR-30-5p/TIA-1 axis in regulating mitochondrial dynamics and cellular senescence.