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Nucleic Acids Res. 2013 Apr;41(7):4241-52. doi: 10.1093/nar/gkt086. Epub 2013 Feb 21.

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

Author information

1
CEA, Institut de Biologie Structurale Jean-Pierre Ebel, Grenoble, France.

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.

PMID:
23435228
PMCID:
PMC3627579
DOI:
10.1093/nar/gkt086
[Indexed for MEDLINE]
Free PMC Article

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