[3S06e] 16. Cell and Tissue Engineering for Biomedical Process Innovation - Part 3

6:10 PM - 6:30 PM JST(9:10 AM - 9:30 AM UTC)

[P03-297] Functional Characterization of Micropeptides from protein-coding Circular RNA in Alzheimer's Disease

○Sulthan Rafi Ibrahim¹, Christopher Marquis¹ (1. UNSW (Australia))

Keywords:

circular RNA,micropeptides,Alzheimer's disease,Differential expression analysis

Circular RNA is a unique class of closed-loop RNA that is more stable than its linear counterpart. Due to this, circular RNA transcripts could theoretically exist longer than mRNA transcripts, which suggests they might be able to express protein for longer or function as a regulatory molecule. Many recent transcriptomic analyses have revealed their regulatory roles in neural development and their dysregulation in neurodegenerative disorders. However, their functional implications in disease progression remain poorly understood. In this study, we investigated the expression pattern of circular RNA transcripts in various publicly available Alzheimer’s datasets. The predicted differentially expressed circRNAs are then identified and subsequently analyzed to get their encoded open reading frames. Experimental validations are done by proving the existence of the predicted circular RNA and its encoded peptides. From our latest findings, we identified a circular RNA transcript hsa_circ_0090585 derived from a gene called SHROOM4 that is consistently upregulated in many Alzheimer’s total RNA-seq datasets compared to healthy controls. This circRNA transcript is also predicted to encode several truncated versions of the SHROOM4 protein, which we refer to as micropeptides. SHROOM4 is an actin-binding protein that has been suggested to act as a regulator that plays a role in synaptic development. We hypothesize that the micropeptides encoded by the circular RNA transcript might interact and disrupt the normal function of the canonical SHROOM4 protein. We have successfully expressed several of these micropeptides and are currently performing functional assays to determine whether they interact with actin and alter cytoskeletal dynamics. We propose that disrupted actin polymerization, which is mediated by these SHROOM4-derived micropeptides, may contribute to abnormal synaptic function and form amyloid plaques in Alzheimer’s disease.