TAILIEUCHUNG - Báo cáo khoa học: Treatment with small interfering RNA affects the microRNA pathway and causes unspecific defects in zebrafish embryos

MicroRNAs (miRNAs) are generated from primary transcripts through sequential processing by two RNase III enzymes, Drosha and Dicer, in association with other proteins. This maturation is essential for their func-tion as post-transcriptional regulators. | ỊFEBS Journal Treatment with small interfering RNA affects the microRNA pathway and causes unspecific defects in zebrafish embryos Xiao-Feng Zhao Anders Fjose Natalia Larsen Jon V. Helvik and 0yvind Drivenes Department of Molecular Biology University of Bergen Norway Keywords dicer maternalmRNA microRNA RNA interference RNAi zebrafish development Correspondence A. Fjose Department of Molecular Biology University of Bergen PO Box 7803 N-5020 Bergen Norway Fax 47 555 89683 Tel 47 555 84331 E-mail 0. Drivenes Department of Molecular Biology University of Bergen PO Box 7803 N-5020 Bergen Norway Fax 47 555 89683 Tel 47 555 84325 E-mail Received 7 December 2007 revised 18 February 2008 accepted 3 March 2008 MicroRNAs miRNAs are generated from primary transcripts through sequential processing by two RNase III enzymes Drosha and Dicer in association with other proteins. This maturation is essential for their function as post-transcriptional regulators. Notably Dicer is also a component of RNA-induced silencing complexes which incorporate either miRNA or small interfering RNA siRNA as guides to target specific mRNAs. In zebrafish processed miRNAs belonging to the miR-430 family have previously been shown to promote deadenylation and degradation of maternal mRNAs during early embryogenesis. We show that injection of one-cellstage zebrafish embryos with siRNA causes a significant reduction in the endogenous levels of processed miR-430 and other miRNAs leading to unspecific developmental defects. Coinjection of siRNA with preprocessed miR-430 efficiently rescued development. This indicates that the abnormalities generally observed in siRNA-treated zebrafish embryos could be due to inhibition of miR-430 processing and or activity. Our results also suggest that the miRNA pathway in mammals under some experimental or therapeutic conditions may be affected by siRNA. doi MicroRNAs miRNAs are small .

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