title: Gene regulation by translational inhibition is determined by Dicer partnering proteins.
abstract: MicroRNAs (miRNAs) are small regulatory RNAs produced by Dicer proteins that regulate gene expression in development and adaptive responses to the environment(1-4). In animals, the degree of base pairing between a miRNA and its target messenger RNA seems to determine whether the regulation occurs through cleavage or translation inhibition(1). In contrast, the selection of regulatory mechanisms is independent of the degree of mismatch between a plant miRNA and its target transcript(5). However, the components and mechanism(s) that determine whether a plant miRNA ultimately regulates its targets by guiding cleavage or translational inhibition are unknown(6). Here we show that the form of regulatory action directed by a plant miRNA is determined by DRB2, a DICER-LIKE1 (DCL1) partnering protein. The dependence of DCL1 on DRB1 for miRNA biogenesis is well characterized(7-9), but we show that it is only required for miRNA-guided transcript cleavage. We found that DRB2 determines miRNA-guided translational inhibition and represses DRB1 expression, thereby allowing the active selection of miRNA regulatory action. Furthermore, our results reveal that the core silencing proteins ARGONAUTE1 (AGO1) and SERRATE (SE) are highly regulated by miRNA-guided translational inhibition. DRB2 has been remarkably conserved throughout plant evolution, raising the possibility that translational repression is the ancient form of miRNA-directed gene regulation in plants, and that Dicer partnering proteins, such as human TRBP, might play a similar role in other eukaryotic systems.
authors.affiliation: School of Biological Sciences, University of Sydney, Macleay Building A12, Sydney, New South Wales 2006, Australia.|Faculty of Agriculture and Environment, University of Sydney, Eveleigh, New South Wales, Australia.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Reis
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Gene
authors.initials: G
authors.lastname: Hart-Smith
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Eamens
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Wilkins
authors.affiliation: School of Biological Sciences, University of Sydney, Macleay Building A12, Sydney, New South Wales 2006, Australia.|Centre for Tropical Crops and Biocommodities, Queensland University of Technology, Brisbane, Queensland 4001, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Waterhouse