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The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs.

Trabucchi, M; Briata, P; Garcia-Mayoral, M; Haase, AD; Filipowicz, W; Ramos, A; Gherzi, R; (2009) The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature , 459 (7249) pp. 1010-1014. 10.1038/nature08025.

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Abstract

Consistent with the role of microRNAs (miRNAs) in down-regulating gene expression by reducing the translation and/or stability of target messenger RNAs, the levels of specific miRNAs are important for correct embryonic development and have been linked to several forms of cancer. However, the regulatory mechanisms by which primary miRNAs (pri-miRNAs) are processed first to precursor miRNAs (pre-miRNAs) and then to mature miRNAs by the multiprotein Drosha and Dicer complexes, respectively, remain largely unknown. The KH-type splicing regulatory protein (KSRP, also known as KHSRP) interacts with single-strand AU-rich-element-containing mRNAs and is a key mediator of mRNA decay. Here we show in mammalian cells that KSRP also serves as a component of both Drosha and Dicer complexes and regulates the biogenesis of a subset of miRNAs. KSRP binds with high affinity to the terminal loop of the target miRNA precursors and promotes their maturation. This mechanism is required for specific changes in target mRNA expression that affect specific biological programs, including proliferation, apoptosis and differentiation. These findings reveal an unexpected mechanism that links KSRP to the machinery regulating maturation of a cohort of miRNAs that, in addition to its role in promoting mRNA decay, independently serves to integrate specific regulatory programs of protein expression.

Type: Article
Title: The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs.
Location: England
DOI: 10.1038/nature08025
Keywords: Animals, Cell Line, Cell Line, Tumor, Cell Proliferation, Humans, Mice, MicroRNAs, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Ribonuclease III, Trans-Activators
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1418613
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