由于小RNA对基因表达的发展和调控有深远影响,所以它们自己的表达同样一定仅限于在正确的时间出现在正确的细胞中的正确的层面上。
Michael Rosenfeld 和Witold Filipowicz的实验室之间的一个合作课题组报告说,RNA结合蛋白KSRP(“KH-型剪接调控蛋白”的缩写)调控一个亚组的微RNA的前体加工。如果这一调控机制被破坏,其效应在增殖、分化和凋亡上就可以被看到。所以,KSRP既参与mRNA的周转,又参与促进mRNA的表达。这项工作揭示了mi-RNA在调控基因表达上的复杂性的另一个层面。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 459, 1010-1014 (18 June 2009) | doi:10.1038/nature08025
The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs
Michele Trabucchi1, Paola Briata2,5, MariaFlor Garcia-Mayoral3, Astrid D. Haase4, Witold Filipowicz4, Andres Ramos3, Roberto Gherzi2,5 & Michael G. Rosenfeld1,5
1 Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, California 92093-0648, USA
2 Istituto Nazionale per la Ricerca sul Cancro (IST), Largo R. Benzi, 10; 16132 Genova, Italy
3 Division of Molecular Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
4 Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
5 These authors contributed equally to this work.
Consistent with the role of microRNAs (miRNAs) in down-regulating gene expression by reducing the translation and/or stability of target messenger RNAs1, the levels of specific miRNAs are important for correct embryonic development and have been linked to several forms of cancer2, 3, 4. 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 complexes5, 6, 7, 8, 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 decay9, 10. 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.