title: Stimulation of pri-miR-18a processing by hnRNP A1.
abstract: Recent evidence suggests that the canonical miRNA processing pathway can b regulated by a number of positive and negative trans-acting factors. This chapter provides an overview of hnRNP A1-mediated regulation of miR-18a biogenesis. Our laboratory has recently established that the multifunctional RNA-binding protein hnRNP A1 is required for the processing of miR-18a at the nuclear of Drosha-mediated processing. By combining structural and functional analysis of RNA, we showed that hnRNP A1 regulates the processing of pri-miR-18a by binding to its terminal loop and reshaping its stem-loop structure, thus allowing for a more effective Drosha cleavage. Furthermore, we linked the event of hnRNP A1-binding to the pri-miR-18a with an unusual phylogenetic sequence conservation of its terminal loop. Bioinformatic and mutational analysis revealed that a number of pri-miRNAs have highly conserved terminal loops, which are predicted to act as landing pads for trans-acting factors influencing miRNA processing. These results underscore a previously uncharacterized role for general RNA-binding proteins as factors that facilitate the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA production and function.
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine,Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Gracjan
authors.initials: G
authors.lastname: Michlewski
authors.forename: Sonia
authors.initials: S
authors.lastname: Guil
authors.forename: Javier F
authors.initials: JF
authors.lastname: Cáceres
mesh_terms: D000818:Animals; D001483:Base Sequence; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D043244:Ribonuclease III / Q000502:physiology
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; C517918:DROSHA protein, human; D043244:Ribonuclease III