Functional analysis of microRNAs as regulators of secretory membrane trafficking

miRNAs are small non-coding RNAs that regulate the expression of target mRNAs in animals and plants. miRNAs affect numerous biological processes, such as development, tumorigenesis, aging or viral infection. In the present study we demonstrate a fluorescence quantitative microscopy-based approach to identify miRNAs, which potentially regulate secretory membrane trafficking. A high-throughput screening of oligonucleotides mimicking 470 human precursor miRNAs and 875 miRNA inhibitors revealed that nearly 10% of human miRNAs might act as regulators of the conventional secretory pathway. The hits were further analyzed by the additional cellular assays, such as integrity of the Golgi complex. Focus on one of the hits - the oncogenic cluster miR-17-92 - has revealed trafficking regulators LDLR and TBC1D2 as novel targets of miR-17. In the perspective, detailed analysis of the identified regulatory miRNAs and their cognate target genes will allow us to build-up post-transcriptional miRNA regulatory networks and to understand how these networks coordinate the secretory membrane trafficking as a global adaptive response system.