Comprehensive and cell-type-based analysis of microRNA profiles and functions in mouse suprachiasmatic nucleus

Circadian rhythm governs a variety of biological processes in essentially all living organisms and microRNAs have been found to play important roles in the post-transcriptional regulation of circadian clocks. However, the microRNA expression profile in mouse central circadian clock – suprachiasmatic nucleus (SCN) is lacking. In this study, we systematically profiled microRNAs in mouse SCN and SCN subtype neurons by high sensitive small RNA sequencing and examined their potential circadian functions. We found that a large fraction of known microRNAs are SCN-specific and 20 of them are also oscillated significantly. Predicted targets of these 20 microRNAs were enriched in circadian rhythm pathway as well. Integrated analysis of microRNA and mRNA revealed 3 clock-related functional modules, demonstrating the regulation roles of miR-24, miR-30, miR-7a, miR-7b, miR125a and miR125b in SCN. Furthermore, we observed distinct microRNA profiles in SCN subtype neurons with divergent regulatory functions, which correlated with their differential spatial distribution. In addition, we also identified a proportion of light-response microRNAs in SCN, one of which was miR-7a. Further experiments showed that miR-7a directly target fos and regulated its translation in SCN. All these observations indicate important circadian regulation roles of microRNA in central circadian clock. Overall design: Examination of miRNA profiles in mouse SCN, hypothalamus and cortex; Examination of circadian miRNA profiles in mouse SCN; Examination of miRNA profiles in mouse SCN subtype neurons (AVP, VIP and CCK neurons); Examination of light-response miRNAs in mouse SCN