MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms
- *Howard Hughes Medical Institute and †Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
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Edited by Joan A. Steitz, Yale University, New Haven, CT, and approved June 23, 2003 (received for review February 10, 2003)
Abstract
MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences. In contrast, small interfering RNAs (siRNAs), which are derived by processing of long double-stranded RNAs and are often of exogenous origin, degrade mRNAs bearing fully complementary sequences. Here, we demonstrate that an endogenously encoded human miRNA is able to cleave an mRNA bearing fully complementary target sites, whereas an exogenously supplied siRNA can inhibit the expression of an mRNA bearing partially complementary sequences without inducing detectable RNA cleavage. These data suggest that miRNAs and siRNAs can use similar mechanisms to repress mRNA expression and that the choice of mechanism may be largely or entirely determined by the degree of complementary of the RNA target.
Footnotes
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↵ ‡ To whom correspondence should be addressed. E-mail: culle002{at}mc.duke.edu.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: CAT, chloramphenicol acetyl transferase; miRNAs, microRNAs; RISC, RNA-induced silencing complex; siRNAs, small interfering RNAs; β-gal, β-galactosidase; CMV, cytomegalovirus; B, bulge; P, perfect; AP, anti-miR-30 perfect; AB, anti-miR-30 bulge.
- Copyright © 2003, The National Academy of Sciences
