Editing MicroRNAome (section)

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<h1>Function of microRNAs</h1>
miRNA function as guide molecules in post-transcriptional genes silencing by base pairing with target mRNAs, which lea to mRNA cleavage or translational repression.&nbsp; With &gt;200 members pre species in higher eukaryotes, miRNAs are one of the largest gene families, accounting for ~1% of the genome11, recent studies have revealed that miRNAs have key roles in diverse regulatory pathways, including control of developmental timing, Haematopoietic cell differentiation, cell signaling, apoptosis, cancer and diseases, and cell proliferation &amp; organ development, and stem cell. 

&nbsp;
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Apoptosis 
Link between miRNAs, growth control and programmed cell death have also come from other species.&nbsp; The phenotype of mir-48; mir-84; mir-241 mutants in C. elegan is one of cellular overgrowth14.&nbsp; In D. rerio, the zygotic removal of Dicer results in a larval growth arrest15.&nbsp; In additional, in M. Musculus, removal of Dicer in the limb mesoderm leads to a dramatic programmed cell death in the developing limb19.&nbsp; 
Drosophila bantam encodes a 21 nucleotide regulatory miRNA that has an anti-apoptotic17 and also regulated growth14.&nbsp; The sequence of bantam miRNA was found to be partially complementary to the 3&rsquo; UTR sequence of its target, the pro-apoptotic gene hid.&nbsp; Mature miRNAs of bantam inhibit cell death by translational repression of the hid miRNAs. 

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Cancer and Diseases
Many miRNAs are de-regulated in primary human tumors18-19.&nbsp; Many human miRNAs are located at genomic regions linked to cancer19.&nbsp; Of particular interest is the mir-17 miRNA cluster, which is in a region on human chromosome 13 that is frequently amplified in B-cell lymphomas18.&nbsp; Another potential link between miRNAs and human disease comes from the identification of an essential cofactor for the miRNA biogenesis enzyme Drosha.&nbsp; This cofactor is encoded by DGCR8, which maps to chromosomal region 22q11.2 which is commonly deleted in DiGeorge Syndrom20.&nbsp; 
In case of leukemia, the case of miRNA involvement is more suggestive.&nbsp; A majority of DNA alterations occur in regions on chromosome 13 that are associated with mantel cell lymphoma and B cell chronic lymphocytic leukemia21.&nbsp; The miR-15a, miR-16 cluster resides in this region, which is now limited to about 30 kb, and lies between exon 2 and 5 of the LEU2 gene.&nbsp; LEU2 has been excluded as the tumor suppressor gene21.&nbsp; Further, miR-15 and miR-16 are frequently down regulated or deleted in CLL which both miRNA genes are acting as tumor suppressor genes will surface.&nbsp; 

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp; &nbsp;&nbsp;&nbsp; &nbsp; Cell Proliferation and Organ Development 
Many miRNAs have intriguing tissue specific or developmental stage specific expression, suggesting they are involved in developmental processes.&nbsp; Organ specific miRNAs have been identified in lung, spleen, liver, heart, and kidney22 - 23, suggesting that miRNAs and found that miR-427 is expressed transiently after mid-blastula transition24.&nbsp; Further, 17 of 24 miRNAs are detected at specific genes of development, and are continuously expressed until tadpole stage. 

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Cell Signaling
miRNA are involved in many aspect of cellular control, including regulation of signaling pathway25-27.&nbsp; One case of miRNA involvement in cell signaling involves insulin signing.&nbsp; In a study designed o reveal possible roles of miRNAs in pancreatic endocrine cells, an islet-specific miRNA (miR-375) was identified from a library of small RNA cloned from pancreatic b-cell line MIN6 and pancreatic a-cell line27.&nbsp; Several other conserved miRNAs other conserved miRNAs were identified but miR-375 is the most abundant miRNA in the pancreatic cell lines MIN6 and TC1.&nbsp; siRNA silencing of Mtpm showed similar effects as the of miR-375, suggesting it could be a target of miR-37527.&nbsp; As a new regulator of insulin signaling miR-375 has the potential to become a new pharmacological target for diabetes therapy.&nbsp; In general, the targets of miRNAs may substantially increase the number of therapeutic targets for those genes involved in disease states.&nbsp;
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Control of Developmental Timing
Interest in the genes controlling developmental timing in C. elegans led to the cloning of the first miRNA, line-4, and the identification of the first miRNA target, lin-1428.&nbsp; The developmental-timing, or heterochronic, pathway regulates stage-specific processes during C. elegans larval development.&nbsp; For example of the C. elegans life form, only at the adult stage, in line-4 mutant animals, the seam cells (the developmental fate of several stem cells in the lateral hypodermis) repeat the cell division pattern that characterized the first larval stage (L1) and fail to differentiate.&nbsp; This mutant phenotype has been interpreted as a heterochronic change with the developmental clock being stuck at the L1 stage.&nbsp; This result indicated that gain-of-function mutations in the line-4 miRNA lead to an identifiable phenotype, whereas loss-of-function mutations in line-14 result in an opposite where the seam cells skip the cell division of the first larval stage25.&nbsp; Three miRAs of the let-7 family, mir-48, mir-84, and mir-241 are act redundantly to control the next developmental transition, from the second larval stage (L2) to the third larval stage (L3)1, 14.&nbsp; The miRNA let-7 identified controls the tradition from the fourth larval stage11 to the adult stage.&nbsp; Those facts bring attend that at least two miRNA families and at least four miRNAs are involved in the control of developmental timing in C. elegans.&nbsp; As the lin-4 and let-7 miRNA families are conserved, they might play similar roles in other organism.&nbsp; 

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Haematopoietic Cell Differentiation
There is scientific hypothesis that miRNAs are transcriptional regulated in different cell types such that there is extensive cross-talk between transcription and posttranscriptional regulation and that distinct miRNAs are active.&nbsp; In the hematopoeitic system, ectopic expression of miR-181, which is highly expressed in thymus and not in most other tissue, increases the fraction of B-lineage cells both in vitro and vivo39.&nbsp; miRNAs also likely play important role in maintaining mature cell function, as has been described in fat and insulin metabolism4.&nbsp; miRNAs are especially abundant in the adult brain, suggesting a key role for them in neuronal functional and plsticity14.&nbsp; 

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Stem Cell
The complex and cellular diversity of the adult brain arises from the proliferation and differentiation of small number of stem cells.&nbsp; This intrinsic state of stem cells depends on their spatial and temporal history and affects their responsiveness to extrinsic signals from the microevironment.&nbsp; Stem cell self-renewal and different along neural and glial lineages are defined by the dynamic interplay between transcription, epigenetic control, and posttranscriptional regulators, including miRNAs.&nbsp; Given the involvement in developmental processes of the few documentation miRNAs, it is not surprising that a number of miRNA genes are preferentially expressed in stem cells, and maybe involved in maintaining the pluripotent state30.&nbsp; 
miRNAs are especially attractive candidates for regulating stem cell elf-renewal and cell fate decisions, as their ability to simultaneously regulate many target privies a means for coordinated control of concerted gene action.&nbsp; Although direct evidence for a functional role for miRNAs in stem cell biology is just emerging, tantalizing hints regarding their involvement based on expression patterns, predicted targets, and over-expression studies suggest that they will be key regulators.&nbsp; For example, in neuron stem cells, miRNAs has been shown by the rescue of brain morphogenesis in maternal-zygotic dicer zebra fish mutants by injection of miR-43012.&nbsp; This demonstrates that an individual miRNA can trigger large scale changes in development, perhaps as a result of global changes in the transcriptiome14.&nbsp; miRNAs may also define regulatory patterning in the developing central nervous system.&nbsp; miRNAs are likely important regulatory for stem cell self-renewal as well as a stem cell differentiate.&nbsp; They down-regulate stem cell maintenance genes and activate lineage-specific genes.&nbsp; These transitions require a raid switch in gene expression profiles.

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Editing MicroRNAome (section)

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