Careful analysis of cases where introduction of additional copies of endogenous genes caused coordinate silencing of both the transgene and the endogenous gene laid the ground work for the discovery of RNA-mediated silencing. Silencing begins with the expression and recognition of double-stranded RNA, which is cleaved into short RNAs that recognize, by complementarity, sequences that are targets for down regulation. An RNA target can be regarded (post-transcriptional gene silencing), but the small RNAs can also direct the sequence-specific modification of DNA and chromatin. RNA-mediated gene silencing in eukaryotes may have originated as surveillance mechanism to protect the organism from transposable elements and viruses and then evolved to specify chromosomal modifications and to regulate expression of a significant fraction of endogenous genes by microRNAs. This review seeks to furnish the student and non-expert with some idea of how RNA-mediated silencing was discovered and a broad overview of the present state of knowledge.
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