RNA/Protein Discordant Expression of Fndc5 in Central Nervous System Is Likely to Be Mediated Through microRNAs.

Abstract

Fibronectin type III domain-containing 5 protein (Fndc5) is responsible for producing a secretory protein termed, "irisin." A modified expression of Fndc5 has been reported in different tissues during development, differentiation processes, as well as in metabolic events such as exercise. One of the important issues to be fixed is whether Fndc5 RNA level and protein content are concerted and modified hand in hand. Therefore, the aim of this study is to assess Fndc5 RNA and protein levels in various tissues of mouse and rat with emphasis on brain. Biopsies from various parts of neonatal and adult mouse and rat tissues were simultaneously assessed for transcript levels of Fndc5 and compared with the respective protein levels at the same time. Data indicated, unlike in muscle, no concerted fluctuations were observed for Fndc5 RNA and protein, especially in brain. Further look at four regions of brain (cerebellum, putamen, hippocampus, and cortex) revealed a similar discrepant expression. To hypothesize whether such discrepancy is arisen by miRNAs, we selected three main miRNAs, which were predicted to target Fndc5 and their expression levels were assessed in central nervous system (CNS) of mouse and hippocampus of rat. miRNA levels showed an antiparallel correlation with protein level of Fndc5, interpreting a putative role in regulating Fndc5 protein content in CNS. This phenomenon may represent the importance of governing Fndc5 content in neural cells, which seems to be crucial for neural function and differentiation.