Mar 25, 2020

Synergism between microRNA-124 and ELAVL3 drives neuronal gene upregulation during direct neuronal reprogramming of human fibroblasts

BioRxiv : the Preprint Server for Biology
Y.-L. LuAndrew S Yoo


Human neurons generated by direct conversion of adult fibroblasts can serve instrumental tools for modeling diseases as well as a platform to study neurogenic processes. Neuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed. A critical component of the miRNA-mediated conversion process is the role of miR-9/9*-124 targeting and repressing anti-neurogenic genes. However, how these miRNAs function beyond the onset of the neuronal program remains unclear. Here, we performed the Argonaute (AGO) HITS-CLIP analysis to map direct target transcripts of miR-9/9*-124 when cells start adopting the neuronal fate during the conversion (reprogramming) process. Surprisingly, we found that miR-124, in particular, targets a suite of genes associated with neuronal differentiation and function, and these targets appeared to be upregulated by miR-124, as knocking down miR-124 function diminished the expression of these targets. A critical example of the upregulated miR-124 target genes is PTBP2, a neuron-enriched RNA-binding protein known to be repressed by its homolog PTBP1. We elected to focus on PTBP2 to gain insights into the mechanism under...Continue Reading

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Microtubule-Associated Proteins
Mutant Proteins

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