Biology subjects

Mo, D.

Publications and source records attributed to Mo, D..

2 recordsLinked to original sources

bioRxiv2018

The role of Aβ circRNA in Alzheimer’s disease

Alzheimers disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (A{beta}) play a crucial role in the pathology of AD. In familial AD, A{beta} is generated from the full-length amyloid precursor protein (APP) via dysregulated proteolytic processing. However, A{beta} biogenesis in case of sporadic AD remains so far elusive. circRNAs are a class of transcripts, which are preferentially expressed in brain. Here, we identified a circRNA (circA{beta}-a) derived from the A{beta}-coding region of the APP gene. circA{beta}-a is expressed in brains of AD and nondementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circA{beta}-a is efficiently translated into a novel A{beta}-related A{beta}175 protein in living cells. Importantly, A{beta}175 was further processed to A{beta} peptides, the hallmark of AD. In summary, our analysis revealed alternative route of A{beta} biogenesis. circA{beta}-a and its corresponding protein might represent novel therapeutic targets for AD treatment.

neuroscience↗

bioRxiv2018

Intron-mediated enhancement boosts Rtn4 circRNA expression: A robust method for exploring circRNA function

CircRNAs are expressed in many important biological processes. Studying their function requires an effective expression method. When we used intron-mediated enhancement (IME) to improve circRNA expression of mouse Rtn4 (Nogo, a key protein in Nogo-Rho pathways) circRNA as a test case, we achieved a 4-6-fold improvement compared to an existing method. We further developed this approach into a general circRNA expression vector pCircRNA-DMo. An unexpected feature of our approach is its ability to promote translation of circRNA into detectable amounts of proteins. Intriguingly, both monomer and multimer repeating peptides can be observed as a result of rolling circle translation of RTN4 circRNA. We also confirmed the presence of both peptide forms in human and mouse brains, highlighting the significance of circRNA translation in vivo. In summary, we demonstrate the significant advantage of IME in enhancing circRNA biogenesis and hence our vector offers a robust platform for exploring potential circRNA peptide-encoding functions.

biochemistry↗