In genetics, microRNAs (miRNA) is a type of approximately 21-23 nucleotides long single-stranded RNA molecule, plays a role in the regulation of gene expression. RNA'lardandır non-coding miRNAs, ie, DNA transcription, protein translation has not been made, but are encoded by genes. Primary transcripts called pri-miRNA processing, before the short stem-loop structures called pre-miRNA, and then transformed into functional miRNA'ya. Mature miRNA molecules to one or more messenger RNA (mRNA) and partial complementary, and the main functions is to set down gene expression. Lee and his colleagues discovered in 1993 by Victor Ambros lab, but the first in 2001 to use the term girimiştir microRNA.
Formation and Processing
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MicroRNA (miRNA) precursor microRNA (pre-miRNA) from occurs, it is a primary microRNA transcript (pri-miRNA'dan) occurs.
genes encoding the processed mature miRNA molecule miRNA'yı much longer. miRNAs before the primary (primary) transcripts, or pri-miRNA as written, these transcripts have a title and poly-A tail. They see the cell nucleus and the pre-miRNA processing is known as a short, 70 nucleotides in length, stem-loop-shaped, precursor (precursor) into structures. The Microprocessor complex processing in animals (Eng. Microprocessor complex) is carried out by a protein complex called. Microprocessor kompleks'te called Drosha nuclease, and double-stranded RNA-binding protein called Pasha has.
Pre-miRNAs by Dicer endonuclease interact with the cytoplasm miRNA'ya turn into mature. Dicer RNA-induced silencing complex at the same time (Eng. RNA-induced Silencing Complex, RISC) formation starts. This complex is responsible for miRNA expression and RNA interference arising from the gene susturmasından.
Way to the formation of miRNA in plants, due to the lack of homologs Drosha'nın hayvanlardakinden a little different, instead, Dicer homologs alone conduct several processing stages. Intronic miRNAs also occur in the formation of stem-loops is not Drosha, Dicer are involved. Significant pattern of DNA or antisense strand can serve as the formation of the miRNA'nın.
For the efficient processing of pre-miRNA'nın, stem-loop structure and 5 ', and the 3' end of the extensions must be single-stranded RNA. This combination of single-stranded RNA, so the length of the motifs is extremely important, for the realization of processing. A bioinformatics analysis of human and fly pri-miRNA'larının, showed the presence of very similar structural regions, these are the basal parts, stems down, called up the stems and loops end, evolutionarily conserved structures on the basis of the thermodynamic profiles of pri-miRNA'nın described. Drosha complex, the RNA molecules about 22 nucleotides remote end ilmikten cuts. Most pre-miRNA'da a loop at the top of a double-stranded structure is not perfect. There are several possible explanations of this selectivity. One possibility, 21 base pairs long, double-stranded RNA enterferon action mechanism of anti-viral response and pass through the cell. One other plausible explanation miRNA'nın thermodynamic profile of the pre-determination of which strand will be included in the Dicer complex.
Dicer pre-miRNA stem-loop after cutting short RNA molecule consists of two complementary, but only one of them is included in the RISC complex. RISC complex is located in an RNase argonaute'un effect of these two 5 'ends, including the complex is more stable than the one chosen. This strand of the strand guide (Eng. guide strand) is called. The other strand, referred to as the anti-guide or passenger strand, is digested in the RISC complex substrate. After the active RISC complex, miRNAs integrate their complementary base pairing with mRNA molecules that cause destruction of mRNA by proteins makes the Argonaut.
Cellular Functions
miRNA'nın is understood that the function of gene regulation. For this purpose, a miRNA complementary to one or more mRNA. Animal miRNAs usually 3 'UTR complementary region, plant miRNAs complementary to portions of the protein-coding mRNAs. protein prevents translation of the mRNA match miRNA'nın sometimes, and sometimes interrupting mRNA (a process similar to RNA interference) makes it easy. Most of the animal protein translation miRNA'sı obstacles, most of works cutting off the plant miRNA'sı the mRNA. DNA methylation of genomic regions corresponding to the miRNAs also may cause the target mRNA. miRNAs themselves a group of complementary proteins (mikroribonükleoproteinler = miRNP) can act together.
first in 1993 by Victor Ambros and his colleagues miRNA'nın effects of C. elegans worm was discovered. The presence of miRNAs have been confirmed in various plants and animals. Eukaryotic miRNA genes in bacteria were similar, they are matched with the mRNA and translation of mRNA controls the crowd, but not part of this process, similar to the Dicer enzyme, in general, these RNAs as miRNA sayılmamaktadırlar.
Plants short interfering RNA (Eng. short-interfering RNA, siRNA is referred to the acronym) used to prevent transcription of viral RNA. Although double-stranded siRNA, a similar mechanism of action closely miRNA'nınkine, hair hairpin structures even more striking considering this similarity. siRNAs in gene control of benefits, such as miRNAs.
Gene Activation
Double-stranded RNA (dsRNA Eng. double-stranded RNA is abbreviated as) also activate the gene expression, this "small RNA induced gene activation" (in English or small RNA-induced gene activation RNAa). With dsRNA targeting the gene promoters, the associated genes may cause a strong activation of transcription. That human cells with the synthetic dsRNA ("etkinleyici small RNA" or Eng. Small activating RNA or Sarna), as well as for endogenous miRNA is shown.
Determination and Manipulation of miRNA signaling
MiRNA'nın a locked nucleic acid type A activity with 2'-O-methyl RNA oligo a morfolino or can be blocked experimentally by using the. miRNA'nın olgunlaşmasındaki steps may be blocked with a blocking oligonucleotide. A miRNA'nın binding site on the mRNA as an oligo can be blocked by the steric hindrance.
miRNA and disease
including the normal function of eukaryotic cells, such as miRNA, defective work miRNA'nın causes the disease. Cancer, neurology, cardiology, viroloji'de in this regard are underway.
miRNA and Cancer
Few relationships were found between miRNA and some types of cancer.
Excessive c-myc (a protein involved in various cancers), which produces a type of mouse studies have shown that miRNA'nın impact the development of cancer. Specifically designed to produce large amounts of miRNAs in lymphoma in mice developed cancer within 50 days and two weeks after they died.
In another study, two types of protein E2F1 regulates cell proliferation was inhibited by miRNA is shown. miRNA, preventing the translation of messenger RNA binding proteins that affect gene activity.
217 genes encoding miRNA activity by measuring gene activity patterns in different cancer types were found ayırdebilen. miRNA profiles may be helpful in the classification of certain cancers. Thus, his doctors whether a cancer in which tissue is spread analzi understand the texture of the original tissue and can plan according to the type of treatment. Chronic lymphocytic leukemia patients who carry the type of developing this cancer is slow to fast is shown to be used to understand miRNA profiling.
miRNA and heart disease
To understand the global role of miRNA function in the mouse heart was blocked and the heart of the miRNA olgulaşması plays an important role in the development of this organ was miRNA'nın. miRNA expression profiling studies demonstrate that the change in expression levels of specific miRNAs in the Diseased human hearts, pointing to their involvement in cardiomyopathies. In addition, the studies of the heart during the development of certain miRNAs miRNAs showed that the different roles.