RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation in vitro. Mus musculus cultivar:N2a

Conformational conversion of cellular prion protein (PrP C ) into infectious PrP (PrP Sc ) is one of the most intriguing processes in modern Biology. It is well accepted that this transition is catalyzed by one or more cofactors that lowers the energy barrier between the different PrP forms. Among all potential candidates, RNA molecules are strong contestants. For nearly two decades, our research group has pursued nucleic acids-both DNA and RNA-capable of inducing PrP misfolding and aggregation. We found that the interaction between recombinant PrP (rPrP) and total RNA extracted from neuroblastoma cells (N2aRNA) results in significant structural alterations. Here, we use rPrP:N2aRNA as a model to search for specific RNA sequences capable of inducing full-length murine rPrP aggregation. N2aRNA was incubated with rPrP and after that, RNA-seq analysis was conducted with RNA isolated from the aggregates using two different protocols. We analyzed thousands of RNA-seq reads, most of them representing ribosomal RNA molecules. The set of recovered molecules is heterogeneous, although specific parts of RNAs involved in ribosomal complex were enriched in the analyzed transcriptome dataset, suggesting that a population of RNAs is responsible for inducing PrP aggregation. Interestingly, analysis of public RNA-seq data of plaques from brain of Alzheimer's Disease mice models revealed some transcripts in common with those found for our PrP study. Although short RNA sequences can induce PrP aggregation, we hypothesize that specific parts of RNA transcripts enriched in low complexity motif sequences can be involved in PrP C binding and conversion to PrP Sc-like species.