title: Transition of a microRNA from repressing to activating translation depending on the extent of base pairing with the target.
abstract: MicroRNAs are major post-transcriptional regulators of gene expression. Here we show in the ancient protozoan Giardia lamblia a snoRNA-derived 26-nucleotide microRNA, miR3, which represses the translation of histone H2A mRNA containing an imperfect target but enhances translation when the target is made fully complementary. A stepwise mutational analysis of the fully complementary target showed that the activating effect of miR3 was significantly reduced when a single nucleotide at the 5'-end of the target was altered. The effect of miR3 became repressive when 12 of the nucleotides lost their complementation to miR3 with maximum repression reached when only 8 base-pairs remained between the miR3 seed sequence and the target. A synthetic 8-nucleotide RNA oligomer of the miR3 seed sequence was found capable of exerting a similar Argonaute-dependent translational repression. This is the first report showing a correlation between the extent of base-pairing with the target and a change in miRNA function.
authors: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
authors: Ashesh A
authors: AA
authors: Saraiya
authors: Wei
authors: W
authors: Li
authors: Ching C
authors: CC
authors: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020029:Base Pairing; D017931:DNA Primers / Q000737:chemistry; D063185:Epigenetic Repression; D005786:Gene Expression Regulation; D016829:Giardia lamblia / Q000235:genetics*; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D014176:Protein Biosynthesis; D020537:RNA, Small Nucleolar / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; D006657:Histones; D035683:MicroRNAs; D020537:RNA, Small Nucleolar