This family represents the
microRNA
Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...
(miRNA) precursor mir-7. This miRNA has been predicted or experimentally confirmed in a wide range of species. miRNAs are transcribed as ~70
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
precursors (modelled here) 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 shor ...
enzyme to give a ~22 nucleotide product. In this case the mature sequence comes from the
5' arm of the precursor. The extents of the
hairpin
A hairpin or hair pin is a long device used to hold a person's hair in place. It may be used simply to secure long hair out of the way for convenience or as part of an elaborate hairstyle or coiffure. The earliest evidence for dressing the ha ...
precursors are not generally known and are estimated based on hairpin prediction. The involvement of Dicer in miRNA processing suggests a relationship with the phenomenon of
RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
.
Mature miRNA-7 is derived from three microRNA precursors in the human genome, miR-7-1, miR-7-2 and miR-7-3. miRNAs are numbered based on the sequence of the mature RNA.
miR-7 is directly regulated by the transcription factor HoxD10.
miRNAs are thought to have regulatory roles through complementarity to mRNA.
miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux.
It plays an important role in controlling mRNA expression. The miR-7 gene is found in most sequenced
Urbilateria species, and the sequence of its mature miRNA product is perfectly conserved from
annelid
The annelids (), also known as the segmented worms, are animals that comprise the phylum Annelida (; ). The phylum contains over 22,000 extant species, including ragworms, earthworms, and leeches. The species exist in and have adapted to vario ...
s to humans, indicating a strong functional conservation.
Targets of miR-7
Bioinformatic predictions suggest that the human EGFR mRNA 3'-untranslated region contains three microRNA-7 (miR-7) target sites, which are not conserved across mammals.
In Drosophila photoreceptor cells, miR-7 controls epidermal growth factor receptor (EGFR) signaling and promotes photoreceptor differentiation.
Among other targets of miR-7 are
insulin-like growth factor 1 receptor
The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2 ...
(IGF1R) and PIK3CD,
E(spl) gene family
[ ] and Pak1 (cancer cells).
c-Fos
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Ji ...
is also a target of miR-7b in mice.
translation in the lateral wall of the
subventricular zone
The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zon ...
of developed mice is post-transcriptionally regulated by miRNA-7a mediated gene silencing, which is necessary to control the rate of
dopaminergic neuron
Dopaminergic cell groups, DA cell groups, or dopaminergic nuclei are collections of neurons in the central nervous system that synthesize the neurotransmitter dopamine. In the 1960s, Dopaminergic pathways, dopaminergic neurons or ''dopamine neuron ...
production in the olfactory bulb.
Clinical relevance
Multiple roles and targets of miR-7 as well as its expression pattern were linked to regulatory mechanisms and pathogenesis in
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
,
breast cancer
and other types of cancers,
as well as in schizophrenia
and visual abnormalities.
Inhibition of the motility, invasiveness, anchorage-independent growth, and tumorigenic potential of highly invasive breast cancer cells through the introduction of miR-7 suggests a strong therapeutic potential of miR-7.
References
Further reading
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External links
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{{miRNA precursor families
MicroRNA
MicroRNA precursor families