Ambros 206 species and has also registered 256 precursor

Ambros
and coworkers discovered the first miRNA, lin-4 RNA, in nematode Caenorhabditis elegans in 1993 as a key
regulator of developmental timing inhibiting lin-14 and lin-28 necessary for
progression to larval stage 2 from stage 1. In 2000, Gary Rubkins lab discovered  let-7 RNA temporally regulating developmental
timinig in C. elegans by
downregulating expression of genes like lin-41and activating larval stage 4 to
adult stage switch. Mutations in the heterochronic genes lin-4 and let-7 cause
temporal modification in cell fates and affect developmental timing. MiRBase is the database resource for miRNA data
and the latest miRBase 21 released in 2014 contains 28645 miRNA loci from 206
species and has also registered 256 precursor
miRNA sequences in D. melanogaster,
1193 in mouse, 250 in C. elegans, 325
in Arabidopsis thaliana and 1881 in
human while 466 mature miRNA sequenes in D.
melanogaster, 1915 in mouse, 434 in C.
elegans, 427 in Arabidopsis thaliana
and 2588 in Homo sapiens. Also, approximately
5600 novel miRNA sequences were added to the human genome according to the
researchers from Thomas Jefferson University in Philadelphia in 2015. These
numbers are gradually increasing reaching tens of thousands of miRNA genes in
mammalian genome as observed from deep-sequencing technologies, specialized
small RNA isolation and cloning procedures.

The first discovered miRNAs, lin-4, let-7, were named after their phenotypes. Subsequently,
miRNAs identified by sequencing or cloning were given numerical names for instance,
homologues of lin-4 in other species
were called mir-125. Furthermore, lettered suffixes were added at the end of
miRNA sisters like mir-125a and mir-125b and numeric suffixes at the end of the
same miRNAs transcribed from multiple separate loci such as mir-125b-1 and
mir-125b-2. Interestingly, mature miRNA generated from 5′ strand is named
miR-125a-5p whereas the one generated from 3′ strand is miR-125a-3p.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

Many
miRNAs are conserved in different species. Humans have at least 277 genes that
fall into 153 conserved families out of which 87 are found in Zebrafish. 33 of
the conserved genes in Zebrafish are also observed in flies suggesting a very
important role in evolution. For example, miR-1 is found in the muscles of
humans, worms and flies with very similar sequences except at the 3′ end.
Moreover, related miRNAs can be found within the species. For instance, 3
different members of miR-1 family are observed in humans, one in flies and two
in worms. The evolutionarily conserved genes when impaired show higher
possibility of causing diseases as these conserved genes can connect more with
other human genes. On the contrary, the most studied plant model, dicot
Arabidopsis has 90 conserved miRNAs that fall into 20 families conserved from
monocots, rice to dicots. Out of these 20, 12 are even found in moss.
Additionally, there are hundreds of non-conserved miRNA genes. Some of the
non-conserved genes at higher levels have species-specific function in humans
whilst most of them are expressed at very low levels making them hard to
detect. All these studies on conservation patterns show that miRNAs play an
essential role in the regulation of the development of species. Moreover, discovery
of the conserved miRNA-targets in multiple species can help to identify core
pathways and mechanisms of species development.

As per the latest miRBase data, 86 experiments have been
carried out so far for all tissues in Homo
sapeins, 50 in D. melanogaster,
and 21 in C. elegans. Some of the
identified miRNAs exhibit
tissue specific or cell specific expression pattern that helps in
differentiation and maintenance of tissue or cellular identity for instance, miR-129/219/330 in brain with minimal
or no expression in other tissues, significant expression of miR-122a in liver
with no expression in non-liver tissues but minute expression in brain and
thymus, etc. However, brain-specific miRNAs, miR-135 and miR-183 are expressed
in some non-brain tissues and pancreas islet-specific miR-375 in organs lined
with epithelium suggesting tissue-specificity as well as general abundance of
miRNAs. Half of
the tissue-specific miRNAs were revealed to be clustered miRNAs like four miRNA genes fixed in the Hox gene clusters of Hox A, B,
C and D are miR-196b, miR-10a, miR-196-2 and miR-10b respectively sharing
expression patterns and regulatory control of transcription as observed from in
situ hybridization
and histochemical staining of miR-10a and Hoxb4. Transcription factor
regulatory networks control gene expression by binding to the promoter regions
of miRNAs. MiR-208, cardiac specific miRNA, found within the introns of alpha
myosin heavy chain (MHC) genes control and downregulate expression of miR-208b
in Beta-MHC host gene. In addition to the healthy individuals, the tissue-specific miRNAs are
also involved in various human diseases like diabetes, cancer, and
cardiovascular disease for instance; miR-15a and miR-16-1 found at fragile
sites in B cell lymphocytic leukemia patient.