Understanding the role of noncoding RNA in the reversible formation of amyloid aggregates
Noncoding RNAs (ncRNAs) have recently emerged as important regulators of essential cellular pathways. These molecules possess remarkable functional divergence, acting as transcription/translation factors, epigenetic regulators and architectural molecules. In general, ncRNAs are thought to “fine-tune” the basic proteomic machinery and enhance cellular adaptability in response to environmental stressors. Regardless of the stimulus (e.g. heat shock, metabolic deprivation or DNA damage), many ncRNAs facilitate a state of proliferative arrest, allowing the cell to focus its resources on pathways critical to its survival. As the list of functional RNA molecules continues to rapidly expand, it is becoming increasingly clear that the significance and functionality of this family of transcripts may someday rival that of proteins.
Our research group studies a newly discovered extracellular stress-response pathway, whereby ncRNAs regulate the rapid and reversible conversion of proteins into amyloid-like structures. Remarkably, these natural amyloids possess most of the biochemical properties associated with the plaques and aggregates observed in Alzheimer’s, Parkinson’s and prion-based diseases, suggesting that dysregulation of this biological pathway could be a common cause of many neurodegenerative disorders. We are focused on identifying the environmental and cellular factors that mediate the formation and disassembly of these natural amyloid aggregates, while considering the translational significance of this work to prevent and treat neurological diseases.
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- Wang M, Audas TE and Lee S. (2017) Disentangling a bad reputation: changing perceptions of amyloids. Trends in Cell Biology. 27(7), 465-467. doi: org/10.1016/j.tcb.2017.03.001.
- Audas TE et al. (2016) Adaptation to Stressors by Systemic Protein Amyloidogenesis. Developmental Cell. 39(2):155-168. doi: 10.1016/j.devcel.2016.09.002.
- Audas TE, Lee S. (2016) Stressing out over long noncoding RNA. Biochim Biophys Acta. 1859(1):184-91. doi: 10.1016/j.bbagrm.2015.06.010.
- Audas TE, Jacob MD, Lee S. (2012) Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA. Molecular Cell. 45(2):147-57. doi: 10.1016/j.molcel.2011.12.012.