miR-155

406947n/an/an/an/an/an/an/an/an/aMiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases. MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases. The MIR155HG was initially identified as a gene that was transcriptionally activated by promoter insertion at a common retroviral integration site in B-cell lymphomas and was formerly called BIC (B-cell Integration Cluster). The MIR155HG is transcribed by RNA polymerase II and the resulting ~1,500 nucleotide RNA is capped and polyadenylated. The 23 nucleotide single-stranded miR-155, which is harbored in exon 3, is subsequently processed from the parent RNA molecule. The MIR155HG RNA transcript does not contain a long open reading frame (ORF), however, it does include an imperfectly base-paired stem loop that is conserved across species. This non-coding RNA (ncRNA) is now defined as a primary-miRNA (pri-miRNA). Once miR-155 pri-miRNA is transcribed, this transcript is cleaved by the nuclear microprocessor complex, of which the core components are the RNase III type endonuclease Drosha and the DiGeorge critical region 8 (DGCR8) protein, to produce a 65 nucleotide stem-loop precursor miRNA (pre-mir-155) (see Figure 2). Following export from the nucleus by exportin-5, pre-mir-155 molecules are cleaved near the terminal loop by Dicer resulting in RNA duplexes of ~22nucleotides. Following Dicer cleavage, an Argonaute (Ago) protein binds to the short RNA duplexes, forming the core of a multi-subunit complex called the RNA-induced silencing complex (RISC). In a manner similar to siRNA duplexes, one of the two strands, the 'passenger miRNA' (miR-155*), is released and degraded while the other strand, designated the 'guide strand' or 'mature miRNA' (miR-155), is retained within the RISC. Recent data suggest that both arms of the pre-miRNA hairpin can give rise to mature miRNAs. Due to the increasing number of examples where two functional mature miRNAs are processed from opposite arms of the same pre-miRNA, pre-mir-155 products are now denoted with the suffix -5p (from the 5′ arm) (e.g. miR-155-5p) and -3p (from the 3′ arm) (e.g. miR-155-3p) following their name (see Figure 3). Once miR-155-5p/-3p is assembled into the RISC, these molecules subsequently recognize their target messenger RNA (mRNA) by base pairing interactions between nucleotides 2 and 8 of miR-155-5p/-3p (the seed region) and complementary nucleotides predominantly in the 3'-untranslated region (3'-UTR) of mRNAs (see Figure 4 and 5 below). Finally, with the miR-155-5p/-3p acting as an adaptor for the RISC, complex-bound mRNAs are subjected to translational repression (i.e. inhibition of translation initiation) and/or degradation following deadenylation. Early phylogenetic analyses demonstrated that the sequence of pre-mir-155 and miR-155-5p was conserved between human, mouse, and chicken. Recent annotated sequencing data found that 22 different organisms including, mammals, amphibians, birds, reptiles, sea squirts, and sea lampreys, express a conserved miR-155-5p. Currently much less sequence data is available regarding miR-155-3p, therefore, it is not clear how conserved this miRNA is across species. Northern blot analysis found that miR-155 pri-miRNA was abundantly expressed in the human spleen and thymus and detectable in the liver, lung, and kidney. Subsequently, polymerase chain reaction (PCR) experiments demonstrated that miR-155-5p was detectable in all human tissues investigated. Sequence analysis of small RNA clone libraries comparing miRNA expression to all other organ systems examined established that miR-155-5p was one of five miRNAs (i.e. miR-142, miR-144, miR-150, miR-155, and miR-223) that was specific for hematopoietic cells including B-cells, T-cells, monocytes and granulocytes. Together these results suggest that miR-155-5p is expressed in a number of tissues and cell types and, therefore, may play a critical role in a wide variety of biological processes, including hematopoiesis Although very few studies have investigated the expression levels of miR-155-3p, Landgraf et al. established that expression levels of this miRNA was very low in hematopoietic cells. Additionally, PCR analyses found that while miR-155-3p was detectable in a number of human tissues the expression levels of this miRNA were 20-200 fold less when compared to miR-155-5p levels. Even though the function of miR-155-3p has been largely ignored, several studies now suggest that, in some cases (astrocytes and plasmacytoid dendritic cells), both miR-155-5p and -3p can be functionally matured from pre-mir-155.