Dr Dylan Kiltschewskij

Although genomes from many edible mushrooms are sequenced, studies on fungal micro RNAs (miRNAs) are scarce. Most of the bioinformatic tools are designed for plants or animals, but the processing and expression of fungal miRNAs share similarities and differences with both kingdoms. Moreover, since mushroom species such as Agaricus bisporus (A. bisporus, white button mushroom) are frequently consumed as food, controversial discussions are still evaluating whether their miRNAs might or might not be assimilated, perhaps within extracellular vesicles (i.e., exosomes). Therefore, the A. bisporus RNA-seq was studied in order to identify potential de novo miRNA-like small RNAs (milRNAs) that might allow their later detection in diet. Results pointed to 1 already known and 37 de novo milRNAs. Three milRNAs were selected for RT-qPCR experiments. Precursors and mature milRNAs were found in the edible parts (caps and stipes), validating the predictions carried out in silico. When their potential gene targets were investigated, results pointed that most were involved in primary and secondary metabolic regulation. However, when the human transcriptome is used as the target, the results suggest that they might interfere with important biological processes related with cancer, infection and neurodegenerative diseases.

Schizophrenia is a neurodevelopmental disorder associated with abnormal dopamine (DA) signalling and disruptions in early brain development. We have shown that developmental vitamin D-deficiency (DVD-deficiency) increases the risk of schizophrenia in offspring and impairs various aspects of brain development in rodents, particularly that of DA neurons, however the molecular basis of these impairments remains unclear. Here, we explore whether small non-coding microRNAs (miRNAs) are involved. miRNAs regulate gene expression post-transcriptionally via translational repression and destabilisation of mRNA. While dysregulation of multiple miRNAs has been reported in post-mortem brain of patients with schizophrenia, the biological pathways affected by these small RNAs are not clear. Here we identified differential expression of 18 miRNAs in DA neurons isolated from DVD-deficient embryos. Three miRNAs were selected for further functional studies of dopaminergic neuron differentiation based on their interactions with transcripts involved in neuronal maturation. In particular, we show upregulation of miR-181c-5p suppresses neurite outgrowth of dopaminergic neurons. These findings provide further evidence that an environmental risk factor for schizophrenia ¿ DVD-deficiency ¿ disrupts the development of DA neurons and suggests increased miRNA expression may be one possible mechanism. This disruption potentially underlies the long-term alterations in DA mediated brain function in DVD-deficient offspring, and by inference in schizophrenia.