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PerspectiveMultilevel Regulation of Gene Expression by MicroRNAs
MicroRNAs (miRNAs) are Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. E-mail: makeyev{at}mcb.harvard.edu (E.V.M.); maniatis{at}mcb.harvard.edu (T.M.)
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22-nucleotide-long noncoding RNAs that normally function by suppressing translation and destabilizing messenger RNAs bearing complementary target sequences. Some miRNAs are expressed in a cell- or tissue-specific manner and may contribute to the establishment and/or maintenance of cellular identity. Recent studies indicate that tissue-specific miRNAs may function at multiple hierarchical levels of gene regulatory networks, from targeting hundreds of effector genes incompatible with the differentiated state to controlling the levels of global regulators of transcription and alternative pre-mRNA splicing. This multilevel regulation may allow individual miRNAs to profoundly affect the gene expression program of differentiated cells. 
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