title: Structural basis of microRNA length variety.
abstract: The biogenesis of human microRNAs (miRNAs) includes two RNA cleavage steps in which the activities of the RNases Drosha and Dicer are involved. miRNAs of diverse lengths are generated from different genes, and miRNAs that are heterogeneous in length are produced from a single miRNA gene. We determined the solution structures of many miRNA precursors and analysed the structural basis of miRNA length diversity using a new measure: the weighted average length of diced RNA (WALDI). We found that asymmetrical structural motifs present in precursor hairpins are primarily responsible for the length diversity of miRNAs generated by Dicer. High-resolution northern blots of miRNAs and their precursors revealed that both Dicer and Drosha cleavages of imperfect specificity contributed to the miRNA length heterogeneity. The relevance of these findings to the dynamics of the dicing complex, mRNA regulation by miRNA, RNA interference and miRNA technologies are discussed.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego, Poznan, Poland.
authors.forename: Julia
authors.initials: J
authors.lastname: Starega-Roslan
authors.forename: Jacek
authors.initials: J
authors.lastname: Krol
authors.forename: Edyta
authors.initials: E
authors.lastname: Koscianska
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
authors.forename: Wojciech J
authors.initials: WJ
authors.lastname: Szlachcic
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sobczak
authors.forename: Wlodzimierz J
authors.initials: WJ
authors.lastname: Krzyzosiak
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D012322:RNA Precursors / Q000737:chemistry* / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors; C517918:DROSHA protein, human; D043244:Ribonuclease III