Mir-96 microRNA
Encyclopedia
miR-96 microRNA precursor is a small non-coding RNA
that regulates gene expression
. microRNAs are transcribed as ~80 nucleotide
precursors and subsequently processed by the Dicer
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. These microRNAs are expressed specifically in the inner ear and the adult eye.
miR-96 is thought to be conserved within Nephrozoa, i.e. the Deuterostome
s and Protostome
s.
Variation within the seed region of mature miR-96 has been associated with autosomal dominant, progressive hearing loss in humans and mice. The homozygous mutant mice were profoundly deaf, showing no cochlea
r responses. Heterozygous
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
, Myrip, Odf2
and Ryk
.
Microarray
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
, Prestin
, Ptprq
and Gfi1
, all of which are strongly and specifically expressed in hair cells. Mice mutant for the latter three exhibit deafness and hair cell degeneration.
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...
that regulates gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
. microRNAs are transcribed as ~80 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
precursors and subsequently processed by the Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...
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. These microRNAs are expressed specifically in the inner ear and the adult eye.
miR-96 is thought to be conserved within Nephrozoa, i.e. the Deuterostome
Deuterostome
Deuterostomes are a superphylum of animals. They are a subtaxon of the Bilateria branch of the subregnum Eumetazoa, and are opposed to the protostomes...
s and Protostome
Protostome
Protostomia are a clade of animals. Together with the deuterostomes and a few smaller phyla, they make up the Bilateria, mostly comprising animals with bilateral symmetry and three germ layers...
s.
Variation within the seed region of mature miR-96 has been associated with autosomal dominant, progressive hearing loss in humans and mice. The homozygous mutant mice were profoundly deaf, showing no cochlea
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
r responses. Heterozygous
Zygosity
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...
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
AQP5
Aquaporin-5 is a protein that in humans is encoded by the AQP5 gene.- External links :...
, Celsr2
CELSR2
Cadherin EGF LAG seven-pass G-type receptor 2 is a protein that in humans is encoded by the CELSR2 gene.-Further reading:...
, Myrip, Odf2
ODF2
Outer dense fiber protein 2, also known as cenexin, is a protein that in humans is encoded by the ODF2 gene.-Further reading:...
and Ryk
Related to receptor tyrosine kinase
The related to receptor tyrosine kinase gene encodes the protein Ryk.-History:The gene encoding mouse RYK was first identified in 1992.Subsequently cDNA encoding the RYK protein have been isolated from the following species.*rat*chicken*Human...
.
Microarray
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
analysis of 4-day old wildtype and mutant mice showed that in the 3' UTR
Three prime untranslated region
In molecular genetics, the three prime untranslated region is a particular section of messenger RNA . It is preceeded by the coding region....
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
LOC4951
Oncomodulin, also known as OCM, is a human gene.-Further reading:...
, Pitpnm1
PITPNM1
Membrane-associated phosphatidylinositol transfer protein 1 is a protein that in humans is encoded by the PITPNM1 gene.-Further reading:...
, Prestin
Prestin
Prestin is a protein that in humans is encoded by the SLC26A5 gene.Prestin is the motor protein of the outer hair cells of the inner ear of the mammalian cochlea. It is highly expressed in the outer hair cells, and is not expressed in the nonmotile inner hair cells...
, Ptprq
PTPRR
Protein tyrosine phosphatase receptor-type R is an enzyme that in humans is encoded by the PTPRR gene.-Further reading:...
and Gfi1
GFI1
Zinc finger protein Gfi-1 is a protein that in humans is encoded by the GFI1 gene.-Interactions:GFI1 has been shown to interact with PIAS3 and RUNX1T1.- External links :...
, all of which are strongly and specifically expressed in hair cells. Mice mutant for the latter three exhibit deafness and hair cell degeneration.