Structural basis of microRNA length variety.
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.
Starega-Roslan
Julia
J
Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego, Poznan, Poland.
Krol
Jacek
J
Koscianska
Edyta
E
Kozlowski
Piotr
P
Szlachcic
Wojciech J
WJ
Sobczak
Krzysztof
K
Krzyzosiak
Wlodzimierz J
WJ
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
D035683:MicroRNAs; D012322:RNA Precursors; C517918:DROSHA protein, human; D043244:Ribonuclease III