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Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 4 October 2023 / Approved: 5 October 2023 / Online: 6 October 2023 (05:46:11 CEST)

A peer-reviewed article of this Preprint also exists.

Lozano-Velasco, E.; Garcia-Padilla, C.; Carmona-Garcia, M.; Gonzalez-Diaz, A.; Arequipa-Rendon, A.; Aranega, A.E.; Franco, D. MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-Transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Member Expression. Non-Coding RNA 2024, 10, 32. Lozano-Velasco, E.; Garcia-Padilla, C.; Carmona-Garcia, M.; Gonzalez-Diaz, A.; Arequipa-Rendon, A.; Aranega, A.E.; Franco, D. MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-Transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Member Expression. Non-Coding RNA 2024, 10, 32.

Abstract

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.

Keywords

Mef2c; microRNAs; RNPs

Subject

Biology and Life Sciences, Biology and Biotechnology

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