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

Matthieu P.M.H. Benoit, Lionel Imbert, Andrés Palencia, Julien Pérard, Christine Ebel, Jérôme Boisbouvier, Michael J. Plevin

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4241-4252
Number of pages12
JournalNucleic acids research
Volume41
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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