What microRNAs could tell us about the human X chromosome
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Cellular and Molecular Life Sciences
REVIEW
What microRNAs could tell us about the human X chromosome Armando Di Palo1 · Chiara Siniscalchi1 · Mariacarolina Salerno2 · Aniello Russo1 · Claus Højbjerg Gravholt3,4 · Nicoletta Potenza1 Received: 19 December 2019 / Revised: 18 March 2020 / Accepted: 13 April 2020 © Springer Nature Switzerland AG 2020
Abstract MicroRNAs (miRNA) are small-non coding RNAs endowed with great regulatory power, thus playing key roles not only in almost all physiological pathways, but also in the pathogenesis of several diseases. Surprisingly, genomic distribution analysis revealed the highest density of miRNA sequences on the X chromosome; this evolutionary conserved mammalian feature equips females with a larger miRNA machinery than males. However, miRNAs contribution to some X-related conditions, properties or functions is still poorly explored. With the aim to support and focus research in the field, this review analyzes the literature and databases about X-linked miRNAs, trying to understand how miRNAs could contribute to emerging gender-biased functions and pathological mechanisms, such as immunity and cancer. A fine map of miRNA sequences on the X chromosome is reported, and their known functions are discussed; in addition, bioinformatics functional analyses of the whole X-linked miRNA targetome (predicted and validated) were performed. The emerging scenario points to different gaps in the knowledge that should be filled with future experimental investigations, also in terms of possible implications and pathological perspectives for X chromosome aneuploidy syndromes, such as Turner and Klinefelter syndromes. Keywords microRNA · X chromosome · Turner syndrome · Klinefelter syndrome
Introduction MicroRNAs (miRNA) are small non-coding RNAs that posttranscriptionally regulate gene expression by affecting both translation and stability of complementary mRNAs [1]. Bioinformatics predictions indicate that mammalian miRNAs regulate 30–50% of all protein-coding genes; each miRNA Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00018-020-03526-7) contains supplementary material, which is available to authorized users. * Nicoletta Potenza [email protected] 1
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Caserta, Italy
2
Pediatric Endocrine Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
3
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
4
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
can bind several mRNAs and each mRNA can be targeted by different miRNAs, thus giving rise to complex regulatory networks that take part in the regulation of almost all physiological pathways [2, 3]. As a consequence, miRNA mutations, dysregulation of their expression or dysfunction of miRNA biogenesis have a key ro
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