MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Members Expression

Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of MADS box family involved in the early development of several cell types including muscle cells. Over the last decade a novel layer of complexity modulating gene regulation is emerging as non-coding RNAs have been identified, impacting in both transcriptional and post-transcriptional regulation. microRNAs represent the most studied and abundantly expressed subtype of small non-coding RNAs and their functional role have been widely documented. On the other hand, our knowledge on the transcriptional and post-transcriptional regulatory mechanisms that drive microRNA expression is still incipient. We recently demonstrated that MEF2C is able to transactive the long, but not short, regulatory element upstream of miR-23a-miR-27a-miR-24-2 transcriptional start site. However, MEF2C over-expression and silencing, respectively, displayed distinct effects on each of the miR-23a-miR-27a-miR-24-2 mature cluster members, without affecting pri-miRNA expression levels, supporting thus additional MEF2C-driven regulatory mechanisms. Within this study we demonstrated a complex post-transcriptional regulatory mechanisms directed by MEF2C in the regulation of miR-23a-miR-27a-miR-24-2 cluster members, distinctly involving different domains of the MEF2C transcription factor and the physical interaction with pre-miRNAs and RNA interacting proteins such as Ksrp, HnRNPa3 and Ddx17.