Progranulin Regulator miR-107 Shows Cross-Species Homology with Plant Viruses (P05.054)

Abstract

Objective: Our hypothesis is that plant viruses augment or suppress endogenous human miRNAs and consequently the target protein-coding genes, thus contributing to the pathogenesis of human disease or helping to preserve health. In the current study, our objective was to uncover plant viruses that are homologous or complementary to human miRNAs. Background Progranulin (PRGN) is a neuroprotective protein that is expressed in both neurons and microglia in the CNS and is associated with frontotemporal lobar degeneration (FTLD) and Alzheimer9s disease (AD). Human microRNAs (miRNA) are short non-coding RNA molecules of 20-23 nucleotides that regulate gene expression. A specific micro RNA, miR-107, is down-regulated in AD and has recently been shown to target PRGN expression. Design/Methods: We performed a Basic Local Alignment Search Tool (BLAST) analysis to find nucleotide sequences similarities in two databases: 1) the moRBase Sequence Database, a repository of published sequences and associated annotation, and 2) the Descriptions of Plant Viruses (DPVweb) genome database. Sequences that showed a statistically significant homology or complementarity of >12 nucleotides (equal or larger than 50% of the average miR length) were selected for functional and gene ontology categorization. Results: miR-107 showed sequence similarity to Grapevine berry virus A (15 base homology), Grapevine berry inner necrosis virus (15 base homology), Soybean dwarf virus (14 base complementarity) and Cymbidium ringspot virus (13 base complementarity). Conclusions: This is the first bioinformatics demonstration of molecular mimicry between plant viruses and human miRNAs. These data support our hypothesis that certain viral nucleotides show sequence homology with a miRNA that has been linked to FTLD and AD. Exposure to plant viruses may influence miR-107 mediated post-transcriptional regulation of PRGN. Finally, the discovery of plant viruses that mimic miR-107 might provide a novel strategy for targeted treatment of FTLD, AD and other neurodegenerative conditions. Disclosure: Dr. Vaishnav has nothing to disclose. Dr. Rebolledo-Mendez has nothing to disclose. Dr. Raha-Chowdhury has nothing to disclose. Dr. Nandi has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Palmer has nothing to disclose. Dr. Cooper has nothing to disclose. Dr. Friedland has nothing to disclose.