User:Tselroy/sandbox
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).[1] 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.[2]
Targets[edit]
Bioinformatic analysis using TargetScan 6.2 (release date June, 2012) [1] revealed at least 4,174 putative human miR-155-5p mRNA targets exist, with a total of 918 conserved sites (i.e. between mouse and human) and 4,249 poorly conserved sites (i.e. human only).[1][3] Although the TargetScan 6.2 algorithm cannot be utilized to determine the miR-155-3p putative targets, one would speculate that this miRNA may also potentially regulate the expression of thousands of mRNA targets. It is important to note that a number of predicted mRNA targets turn out to be false while others are overlooked entirely.
A comprehensive list of miR-155-5p/mRNA targets that were experimentally authenticated by both the demonstration of endogenous transcript regulation by miR-155-5p and validation of the miR-155-5p seed sequence through a reporter assay was recently assembled.[4] This list was comprised of 140 genes and included regulatory proteins for myelopoiesis and leukemogenesis (e.g. AICDA, ETS1, JARID2, SPI1, etc.), inflammation (e.g. BACH1, FADD, IKBKE, INPP5D, MYD88, RIPK1, SPI1, SOCS, etc.) and known tumor suppressors (e.g. CEBPβ, IL17RB, PCCD4, TCF12, ZNF652, etc.).[4] The validated miR-155-5p binding site harbored in the SPI1 mRNA[5] and the validated miR-155-3p binding site harbored in the IRAK3 mRNA [6] are shown in Figures 4 and 5 respectively.
- ^ a b Friedman RC, Farh KK, Burge CB, Bartel DP (January 2009). "Most mammalian mRNAs are conserved targets of microRNAs". Genome Res. 19 (1): 92–105. doi:10.1101/gr.082701.108. PMC 2612969. PMID 18955434.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Cite error: The named reference
Fabianwas invoked but never defined (see the help page). - ^ Lewis BP, Burge CB, Bartel DP (January 2005). "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets". Cell. 120 (1): 15–20. doi:10.1016/j.cell.2004.12.035. PMID 15652477.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ a b Neilsen PM, Noll JE, Mattiske S, Bracken CP, Gregory PA, Schulz RB, Lim SP, Kumar R, Suetani RJ, Goodall GJ, Callen DF (July 2012). "Mutant p53 drives invasion in breast tumors through up-regulation of miR-155". Oncogene. 32 (24): 2992–3000. doi:10.1038/onc.2012.305. PMID 22797073.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, Das PP, Miska EA, Rodriguez A, Bradley A, Smith KG, Rada C, Enright AJ, Toellner KM, Maclennan IC, Turner M (December 2007). "microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells". Immunity. 27 (6): 847–59. doi:10.1016/j.immuni.2007.10.009. PMC 4135426. PMID 18055230.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Zhou H, Huang X, Cui H, Luo X, Tang Y, Chen S, Wu L, Shen N (December 2010). "miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells". Blood. 116 (26): 5885–94. doi:10.1182/blood-2010-04-280156. PMID 20852130.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)