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As we trek into the uncharted territories of the genomic era, there is an urgency for the development of approaches for assigning functions to the multitude of uncharacterized genes. Although currently available knock-out methodologies could be used for uncovering the function of newly discovered genes, the mixed outcomes in terms of the success of these approaches in down-regulating gene expression necessitate the development of new functional genomics tools. This chapter describes in detail the experimental method for targeted mRNA degradation inside plant cells by enticing the endogenous and ubiquitous RNase P into recognition of specific mRNAs as non-natural substrates.