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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.

Targets
Bioinformatic analysis using TargetScan 6.2 (release date June, 2012) 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). 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. 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.). The validated miR-155-5p binding site harbored in the SPI1 mRNA and the validated miR-155-3p binding site harbored in the IRAK3 mRNA are shown in Figures 4 and 5 respectively.