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MicroRNA biogenesis and regulation of bone remodeling

DOI: 10.1186/ar3325

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Transcription factors, RNA binding proteins, and microRNAs (miRNAs) are among the factors that must act coordinately to control gene expression networks important for cellular function [1]. Following transcription, mRNAs are subject to the processes of splicing, nuclear export, trafficking, and polyadenylation, followed by translation initiation and elongation. Each of these processes represents a point at which expression can be regulated, allowing for fine-tuning in response to changing environmental conditions. miRNAs are short (approximately 21-nucleotide) non-coding RNAs that regulate transcript localization, polyadenylation, and translation. miRNAs are direct negative regulators of gene expression that bind to specific sequences within a target mRNA [2,3].miRNAs were discovered as a result of studies aimed at identifying genes that mediate developmental transitions in Caenorhabditis elegans [4,5]. Recent years have seen significant advances in the miRNA field, including the characterization of the miRNA biogenesis pathway, identification of the mechanisms by which miRNAs regulate gene expression, and an appreciation of how families of miRNAs can regulate cellular processes and contribute to disease phenotypes.The goal of this review is to highlight our current understanding of miRNA biogenesis and mechanisms of action, and to summarize recent studies on the role of miRNAs in bone remodeling.The miRNA biogenesis pathway has several steps: transcription, pri-miRNA processing, transport to the cytoplasm, precursor miRNA (pre-miRNA) processing, strand selection, transcript targeting, and transcript fate (Figure 1). This rigorous, multistep processing pathway helps ensure that only RNAs with the correct structures and sequences are able to regulate gene expression.miRNA genes are found on every chromosome in humans, except for the Y chromosome. Like the promoters of protein-coding genes, miRNA promoters are regulated by epigenetics and by transcription factors. miR

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