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The RNA-binding region of human TRBP interacts with microRNA precursors through two independent domains

Abstract : MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through RNA interference. Human miRNAs are generated through a series of enzymatic processing steps. The precursor miRNA (pre-miRNA) is recognized and cleaved by a complex containing Dicer and several non-catalytic accessory proteins. HIV TAR element binding protein (TRBP) is a constituent of the Dicer complex, which augments complex stability and potentially functions in substrate recognition and product transfer to the RNA-induced silencing complex. Here we have analysed the interaction between the RNA-binding region of TRBP and an oncogenic human miRNA, miR-155, at different stages in the biogenesis pathway. We show that the region of TRBP that binds immature miRNAs comprises two independent double-stranded RNA-binding domains connected by a 60-residue flexible linker. No evidence of contact between the two double-stranded RNA-binding domains was observed either in the apo- or RNA-bound state. We establish that the RNA-binding region of TRBP interacts with both pre-miR-155 and the miR-155/miR-155* duplex through the same binding surfaces and with similar affinities, and that two protein molecules can simultaneously interact with each immature miRNA. These data suggest that TRBP could play a role before and after processing of pre-miRNAs by Dicer.
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Contributeur : Frank Thomas <>
Soumis le : jeudi 26 mai 2016 - 08:24:37
Dernière modification le : mercredi 14 octobre 2020 - 04:17:51

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Matthieu Benoit, Lionel Imbert, A. Palencia, J. Perard, Christine Ebel, et al.. The RNA-binding region of human TRBP interacts with microRNA precursors through two independent domains. Nucleic Acids Research, Oxford University Press, 2013, 41 (7), pp.4241-4252. ⟨10.1093/nar/gkt086⟩. ⟨hal-01321558⟩



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