The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis - PubMed (original) (raw)

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The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis

Leonidas Benetatos et al. Cell Mol Life Sci. 2013 Mar.

Abstract

The mammalian genome is transcribed in a developmentally regulated manner, generating RNA strands ranging from long to short non-coding RNA (ncRNAs). NcRNAs generated by intergenic sequences and protein-coding loci, represent up to 98 % of the human transcriptome. Non-coding transcripts comprise short ncRNAs such as microRNAs, piwi-interacting RNAs, small nucleolar RNAs and long intergenic RNAs, most of which exercise a strictly controlled negative regulation of expression of protein-coding genes. In humans, the DLK1-DIO3 genomic region, located on human chromosome 14 (14q32) contains the paternally expressed imprinted genes DLK1, RTL1, and DIO3 and the maternally expressed imprinted genes MEG3 (Gtl2), MEG8 (RIAN), and antisense RTL1 (asRTL1). This region hosts, in addition to two long intergenic RNAs, the MEG3 and MEG8, one of the largest microRNA clusters in the genome, with 53 miRNAs in the forward strand and one (mir-1247) in the reverse strand. Many of these miRNAs are differentially expressed in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of this vital genomic region, and examine the role the microRNAs of this region may play in controlling tissue homeostasis and in the pathogenesis of some human diseases, mostly cancer, when aberrantly expressed. The potential clinical implications of this data are also discussed.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Fig. 1

Fig. 1

Schematic representation of the DLK1-DIO3 genomic region in the parental and maternal chromosomes. Genes, miRNAs, snoRNAs, lincRNAs, and pseudogenes are noted

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References

    1. Shabalina SA, Spiridonov NA. The mammalian transcriptome and the function of non-coding DNA sequences. Genome Biol. 2004;5(4):105. doi: 10.1186/gb-2004-5-4-105. - DOI - PMC - PubMed
    1. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol. 2010;220(2):126–139. doi: 10.1002/path.2638. - DOI - PubMed
    1. Mattick JS. The genetic signatures of noncoding RNAs. PLoS Genet. 2009;5(4):e1000459. doi: 10.1371/journal.pgen.1000459. - DOI - PMC - PubMed
    1. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10(2):126–139. doi: 10.1038/nrm2632. - DOI - PubMed
    1. Rother S, Meister G. Small RNAs derived from longer non-coding RNAs. Biochimie. 2011;93(11):1905–1915. doi: 10.1016/j.biochi.2011.07.032. - DOI - PubMed

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