PDF(Pubmed)
Abstract：
Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of the 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 has emerged as non-coding RNAs have been identified, impacting both transcriptional and post-transcriptional regulation. microRNAs represent the most studied and abundantly expressed subtype of small non-coding RNAs, and their functional roles have been widely documented. On the other hand, our knowledge of the transcriptional and post-transcriptional regulatory mechanisms that drive microRNA expression is still incipient. We recently demonstrated that MEF2C is able to transactivate the long, but not short, regulatory element upstream of the 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, thus supporting additional MEF2C-driven regulatory mechanisms. Within this study, we demonstrated a complex post-transcriptional regulatory mechanism 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 Ksrp, HnRNPa3 and Ddx17 transcripts.
摘要：
转录调控是基因表达调控的关键步骤。肌细胞增强因子2C（MEF2C）是MADS盒家族的转录因子，参与几种细胞类型的早期发育，包括肌肉细胞.在过去的十年里，随着非编码RNA的鉴定，一个新的复杂的基因调控层已经出现，影响转录和转录后调控。microRNAs代表了研究最多、表达最丰富的非编码小RNA亚型，他们的功能角色已经被广泛记录。另一方面,我们对驱动microRNA表达的转录和转录后调控机制的了解仍处于初期。我们最近证明了MEF2C能够长期激活，但不短，miR-23a-miR-27a-miR-24-2转录起始位点上游的调控元件。然而,MEF2C过表达和沉默，分别,在不影响pri-miRNA表达水平的情况下，对每个miR-23a-miR-27a-miR-24-2成熟簇成员表现出不同的作用，从而支持额外的MEF2C驱动的监管机制。在这项研究中，我们在miR-23a-miR-27a-miR-24-2簇成员的调控中展示了由MEF2C指导的复杂的转录后调控机制,明显涉及MEF2C转录因子的不同结构域以及与pre-miRNAs和Ksrp的物理相互作用，HnRNPa3和Ddx17转录物。
