Predicting and validating microRNA targets 英文参考文献.docVIP

Opinion Predicting and validating microRNA targets Eric C Lai Address: 545 Life Sciences Addition, Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720-3200, USA. E-mail: lai@ Published: 31 August 2004 Genome Biology 2004, 5:115 The electronic version of this article is the complete one and can be found online at /2004/5/9/115 ? 2004 BioMed Central Ltd Abstract Given that microRNAs select their targets by nucleotide base-pairing, it follows that it should be possible to find microRNA targets computationally. There has been considerable progress, but assessing success and biological significance requires a move into the ‘wet’ lab. Traditional thinking regarding gene regulation was shaken by the recent discovery of microRNAs (miRNAs), an abun- dant class of endogenous 21-22-nucleotide RNAs that mediate post-transcriptional regulation via components of the RNA-interference (RNAi) pathway, either by directing target transcript cleavage or by translational inhibition (Figure 1a) [1,2]. Early miRNA discovery relied upon cloning and sequencing of small RNAs to find those whose corre- sponding genomic loci adopted an extended hairpin struc- ture as RNA; such a structure is an obligate precursor to the mature miRNA. Effective computational methods were later developed that recognize miRNA precursors as a particular class of evolutionarily conserved RNA hairpins. Hundreds of different miRNAs have now been identified in complex eukaryotes, implying that they mediate a vast network of unappreciated regulatory interactions. Nevertheless, the in vivo functions and biologically relevant target genes are thus far known only for a few miRNAs. Given that target selection is guided by the miRNA sequence, can miRNA targets be predicted informatically? ity of these predicted target sites was argued large