Somel M, Liu X, Tang L, Yan Z, Hu H, Guo S, Jiang X, Zhang X, Xu G, Xie G, Li N, Hu Y, Chen W, Pääbo S, Khaitovich P. MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates. PLoS Biol. 2011 Dec;9(12):e1001214. PubMed.
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Laval University
In this somewhat “hard-core” transcriptomics study, the authors propose that human-specific gene expression changes that occur during brain development (in what the authors define as “type III” genes) are regulated mainly by transregulatory elements, and, in particular, non-protein-coding microRNAs (miRNAs or miRs). MicroRNAs, a large and abundant class of regulatory RNAs, function in gene silencing and are important for neuronal function and survival. The authors also identified miRNAs that correlated negatively with a subset of type III neuronal genes. Among these, they focused on three: miR-92a, miR-454, and miR-320b, which are highly conserved among humans, chimpanzees, and macaques. When overexpressed in human neuroblastoma cells, candidate miRNAs could indeed regulate predicted target genes.
Notably, two out of three candidate miRNAs could regulate genes associated with calcium signaling, known to be important for synaptic plasticity and memory formation. Importantly, the authors could show that miR-320b is expressed in neuronal cells in humans and in macaques in vivo, although expression levels seemed quite low, which is line with deep-sequencing data in humans (miRBase.org). It should be noted that humans, like the macaque and the chimp, express mainly the 3’ arm (-3p) of miR-92a and miR-454 precursors. Unfortunately, it is not clear which miRNA sequence (either 3p or 5p) was used in the functional analyses described in the study. This is important, as 3’ and 5’ arms of the same miRNA have different sequences, and thus could target different genes.
Certainly, this study opens the door to various validation and functional studies, and provides good candidates for future studies aimed at understanding the role of miRNAs in age-related neurodegenerative disorders.
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