Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans

Pontual, Loïc de; Yao, Evelyn; Callier, Patrick; Faivre, Laurence; Drouin, V; Cariou, Sandra; Haeringen, Arie van; Geneviève, David; Goldenberg, Alice; Oufadem, Myriam; Manouvrier, Sylvie; Münnich, Arnold; Vidigal, Joana A.; Vekemans, Michel; Lyonnet, Stanislas; Henrion‐Caude, Alexandra; Ventura, Andrea; Amiel, Jeanne

doi:10.1038/ng.915

Cited by 275 publications

(286 citation statements)

References 35 publications

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“…Similarly, the miR-17B92 cluster, comprising six well-studied miRNAs, has been tied to skeletal defects in humans. De Pontual et al 33 uncovered hemizygous deletions of the miRNA cluster in patients with microcephaly, featuring shortened stature and digital abnormalities, and miR-17B92 heterozygous mice phenocopy the human developmental features.…”

Section: Mirna Regulation Of Other Bone-related Pathologiesmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in regulating gene expression through the disruption of target genes. The miRNA-induced suppression can occur through Argonaute-mediated cleavage of target mRNAs or by translational inhibition. System-wide studies have underscored the integral role that miRNAs play in regulating the expression of essential genes within bone marrow stromal cells. The miRNA expression has been shown to enhance or inhibit cell differentiation and activity, and elucidating miRNA targets within bone marrow cells has revealed novel regulations during normal bone development. Importantly, multiple studies have shown that miRNA misexpression mediates the progression of bone-related pathologies, including osteopetrosis and osteoporosis, as well as the development and progression of osteosarcoma. Furthermore, recent studies have detailed the capacity for miRNAs to influence bone metastasis from a number of primary carcinomas. Taken together, these findings reveal the significant clinical potential for miRNAs to regulate bone homeostasis, as well as to mediate bone-related pathologies.BoneKEy Reports 3, Article number: 549 (2014) | doi:10.1038/bonekey.2014.44 MiRNA Biogenesis and FunctionThe past decade has seen a torrent of novel research into the post-translational regulation of genes via microRNA-mediated suppression. The microRNAs (miRNAs) are a class of B22-nucleotide-long RNAs that repress gene expression through complementary binding to sites in the 3 0 -untranslated region (UTR) of target mRNAs. 1 Mature miRNAs are generated by the sequential cleavage of longer precursor transcripts, or pri-miRNAs, that are typically transcribed from intragenic or intergenic regions by RNA polymerase II. 2 The initial cleavage step, mediated by Drosha and the DGCR8 complex, occurs in the nucleus and produces a shortened (70-100 nucleotides) pre-miRNA hairpin. Pre-miRNAs are exported from the nucleus by Exportin 5, followed by a second cleavage by the ribonuclease Dicer that produces a double-stranded, B18-25-nucleotide-long mature miRNA. One miRNA strand will then combine with Argonaute (AGO2) proteins to produce an RNAinduced silencing complex, allowing for directed pairing with target mRNAs. 1

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Section: Mirna Regulation Of Other Bone-related Pathologiesmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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“…MicroRNAs have been linked to various growth and developmental defects in humans. Deletion of the miR-17~92 cluster has been associated with skeletal and growth defects in humans [54]. miRNAs also regulate the development of nervous system and neural miRNAs like miR-124, miR-132, miR-134 and miR138 have been shown to be involved in the synaptic development and synapse maturation [55,56].…”

Section: Role Of Mirnas In Diseasesmentioning

confidence: 99%

Recent developments in understanding the mechanism and functions of microRNAs

Muzaffar¹,

Bisht²

2017

J App Biol Biotech

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Based on their mechanism of action and biological function, several classes of small RNAs have come into the limelight in the last two decades. These small RNA molecules generally belong to three main categories: short interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs). miRNAs and siRNAs are distinguished primarily because miRNAs are endogenous in nature and are expressed by an organism's own genome, whereas siRNAs are exogenous in origin and derived mainly from the viruses and transposons. The first miRNA, lin-4, was discovered in 1993 as an endogenous regulator of genes that control developmental timing in Caenorhabditis elegans. miRNAs are coded by both plant and animal genomes and their transcription is typically performed by RNA polymerase II. MicroRNAs repress the expression of many genes by accelerating messenger RNA degradation as well as translational inhibition, thereby reducing the level of protein. Due to their involvement in various diseases like cancer, miRNAs have been a focus of scientific research for their potential as a new generation of drugs. The recent findings in miRNA research have been summarized in this review to add new dimensions to miRNA mechanism and functions.

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“…Haploinsufficiency of the DGCR8 gene, which encodes a miRNA-processing factor located within the 22q11.2 chromosomal region that is deleted in DiGeorge syndrome, likely contributes to the cognitive and behavioral phenotypes observed in this disease [20]. Deletion of MIR17HG, which encodes the miR-17-92 cluster, causes Feingold syndrome 2, a disorder characterized by IDD, microcephaly, and other malformations [21]. Disruption of the LINC00299 lncRNA gene also produces a form of IDD [22].…”

Section: Gene Mutations and Other Genomic Featuresmentioning

confidence: 99%

Epigenetic Mechanisms Underlying the Pathogenesis of Neurogenetic Diseases

Qureshi

Mehler

2014

Neurotherapeutics

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There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other healthrelated phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

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Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans

Cited by 275 publications

References 35 publications

MicroRNAs as regulators of bone homeostasis and bone metastasis

MicroRNAs as regulators of bone homeostasis and bone metastasis

Recent developments in understanding the mechanism and functions of microRNAs

Epigenetic Mechanisms Underlying the Pathogenesis of Neurogenetic Diseases

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