Human diseases caused by germline and somatic abnormalities in microRNA and microRNA‐related genes

Abstract

The human genome harbors approximately2000 genes that encode microRNAs (miRNAs), small noncoding RNAs of approximately 20-22 nt that mediate posttranscriptional gene silencing. MiRNAs are generated from long transcripts through stepwise processing by the Drosha/ DGCR8, Exportin-5/RanGTP and Dicer/TRBP complexes. Given that the expression of each individual miRNA is tightly regulated, the altered expression of certain miRNAs plays a pivotal role in human diseases. For instance, germline and somatic mutations in the genes encoding the miRNA processing machinery have been reported in different cancers. Furthermore, certain miRNA genes are encoded within regions that are deleted or duplicated in individuals with chromosomal abnormalities, and the fact that the knockout of these miRNAs in animal models results in lethality or the abnormal development of certain tissues indicates that these miRNA genes contribute to the disease phenotypes. It has also been reported that mutations in miRNA genes or in miRNA-binding sites, which result in the impairment of tight regulation of target mRNA expression, cause human genetic diseases, although these cases are rare. This is in contrast to the aberrant expression of certain miRNAs that results from the impairment of transcriptional or post-transcriptional regulation, which has been reported frequently in various human diseases. The present review focuses on human diseases caused by mutations in genes encoding miRNAs and the miRNA processing machinery as well as in miRNA-binding sites. Furthermore, human diseases caused by chromosomal abnormalities that involve the deletion or duplication of regions harboring genes that encode miRNAs or the miRNA processing machinery are also introduced.

Genetic, environmental, and epigenetic factors involved in CAKUT

“…They hybridize to complementary sites in the 3'-untranslated region of their target mRNAs through their 5'-proximal seed sequence in order to direct mRNA degradation or inhibit protein translation. 74 To date, dysregulation of miRNAs by chromosomal imbalances has mainly been linked to cancers, such as Wilms tumour, where loss of heterozygosity at 2q37 results in a heterozygous deletion of miR-562, which targets EYA1, a renal developmental gene. 75 Autosomal dominant progressive hearing loss was the first example of a Mendelian disease associated with a point mutation in an miRNA.…”

Mesenchymal stem cells as novel micro‐ribonucleic acid delivery vehicles in kidney disease

“…However, since then, unique and conserved miRNAs have been discovered in other animals and plants . In the human genome, approximately 2000 miRNAs have been identified, and these are involved in the regulation of up to 30% of all mammalian protein‐encoding genes . These miRNAs have diverse roles in the cell cycle, apoptosis, tissue development, stem cell division and disease (review,).…”

Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

“…miRNA biogenesis initiates in the nucleus with transcription of the primary miRNA transcript and with several processing steps, and it ends in the cytoplasm with the formation of mature miRNA molecules [8]. In human genome approximately 2000 genes encodes multiple miRNAs that target nearly 60% of all human genes in a sequence-specific manner and modulates gene expression either by mRNA degradation or repression [1, 9–10]. Besides their role as modulator of cellular activity, in pathological and non-pathological states, miRNAs are also released from the cells and enter into circulatory bio-fluids, such as the blood, serum, plasma, saliva, and urine [2, 11].…”