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__NOTOC__ miR-96 microRNA precursor is a small
non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-c ...
that regulates
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
.
microRNAs MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miR ...
are transcribed as ~80
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
precursors and subsequently processed by the
Dicer Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short d ...
enzyme to give a ~23 nucleotide products. In this case the mature sequence comes from the 5′ arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. miR-96 is thought to be conserved withi
Nephrozoa Nephrozoa is a major clade of bilaterians, divided into the protostomes and the deuterostomes, containing almost all animal phyla and over a million extant species. Its sister clade is the Xenacoelomorpha. The Ambulacraria (conventionally deut ...
target="_blank" class="mw-redirect" title="">
Nephrozoa], i.e. the
Deuterostome Deuterostomia (; in Greek) are animals typically characterized by their anus forming before their mouth during embryonic development. The group's sister clade is Protostomia, animals whose digestive tract development is more varied. Some exampl ...
s and
Protostome Protostomia () is the clade of animals once thought to be characterized by the formation of the organism's mouth before its anus during embryonic development. This nature has since been discovered to be extremely variable among Protostomia's memb ...
s. Variation within the seed region of mature miR-96 has been associated with
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
, progressive hearing loss in humans and mice. The
homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
mutant mice were profoundly deaf, showing no
cochlea The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory org ...
r responses.
Heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
mice and humans progressively lose the ability to hear. Five genes, of 132 predicted targets, have been experimentally validated as targets of miR-96: Aqp5,
Celsr2 Cadherin EGF LAG seven-pass G-type receptor 2 is a protein that in humans is encoded by the ''CELSR2'' gene. The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consis ...
, Myrip,
Odf2 Outer dense fiber protein 2, also known as cenexin, is a protein that in humans is encoded by the ''ODF2'' gene. The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm ta ...
and Ryk.
Microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...
analysis of 4-day old wildtype and mutant mice showed that in the 3′ UTR of upregulated genes, there was a significant enrichment in heptamers complementary to miR-96, implying that miR-96 normally affects a wide range of target genes, and that the mutation results in a loss of normal targets. Among the downregulated genes, there is a significant enrichment in heptamers complementary to the mutant miR-96, so the mutant miR-96 has gained novel targets. Among the downregulated genes were five of particular interest; Ocm,
Pitpnm1 Membrane-associated phosphatidylinositol transfer protein 1 is a protein that in humans is encoded by the ''PITPNM1'' gene. Function PITPNM1 belongs to a family of proteins that share homology with the Drosophila retinal degeneration B (rdgB) p ...
,
Prestin Prestin is a protein that is critical to sensitive hearing in mammals. It is encoded by the ''SLC26A5'' (solute carrier anion transporter family 26, member 5) gene. Prestin is the motor protein of the outer hair cells of the inner ear of the mamm ...
,
Ptprq Receptor tyrosine phosphatases are enzyme-linked receptor phosphatases, a sub-class of protein tyrosine phosphatases. Types include PTPRA, PTPRB, PTPRC, PTPRD, PTPRE, PTPRF, PTPRG, PTPRH, PTPRJ, PTPRK, PTPRM, PTPRN, PTPRN2, PTPR ...
and
Gfi1 Zinc finger protein Gfi-1 is a transcriptional repressor that in humans is encoded by the ''GFI1'' gene. It is important normal hematopoiesis. Interactions GFI1 has been shown to interact Advocates for Informed Choice, doing business as, ...
, all of which are strongly and specifically expressed in hair cells. Mice mutant for the latter three exhibit deafness and hair cell degeneration.


References


Media reports


Sanger press release

New Insights Into Progressive Hearing Loss


Further reading

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External links

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miRBase page for the mir-96 microRNA precursor family

HGNC page for the mir-96 microRNA precursor family

OMIM page for the mir-96 microRNA precursor family

ENTREZ page for the mir-96 microRNA precursor family
{{miRNA precursor families Non-coding RNA MicroRNA