MRC National Institute for Medical Research, London
Science for Health
mRNA decay factor regulates miRNA biogenesis
26 May 2009
miRNAs are an important class of small non-coding RNAs that regulate translation and stability of their mRNA targets. In humans about 700 miRNAs influence the expression of more than a third of all genes, with many miRNA targeting multiple genes but also more than one miRNA targeting the same gene. Changes in the level of specific miRNAs have been associated with a number of cancer pathologies. miRNA levels are regulated both at the transcriptional and post-transcriptional stage: the mature miRNA sequence is transcribed as part of a much longer RNA that is then processed by the Microprocessor and Dicer complexes.
Andres Ramos (pictured), from NIMR's Division of Molecular Structure, and colleagues from groups at UCSD, the Italian Cancer Research Institute and the Friedrich Miescher Institute for Biomedical Research, have shown that KSRP, a protein involved in mRNA degradation, promotes the maturation of a cohort of miRNAs and influences proliferation and differentiation of specific cell types. Specificity of the mechanism is provided by KSRP's recognition of the apical loop of the miRNA(s) precursors. A detailed example of the regulatory mechanism is provided for the Let-7 miRNA where KSRP acts antagonistically to Lin28, a protein inhibiting processing of the Let-7 precursor.
This work exemplifies how multi-domain RNA-binding proteins regulate the concentration of specific miRNAs at the post-transcriptional level, and suggests a way that we may be able to control the changes in levels of miRNA that are associated with human cancers.
Dr Ramos
Original article
The research findings are published in full in:
Michele Trabucchi, Paola Briata, MariaFlor Garcia-Mayoral, Astrid D. Haase, Witold Filipowicz, Andres Ramos, Roberto Gherzi & Michael G. Rosenfeld (2009)
The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs
Nature Epub ahead of print. Publisher abstract
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