MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms
Yan Zeng,Rui Yi,Bryan R. Cullen +2 more
TLDR
It is demonstrated 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 RNA bearing partially complementary sequences without inducing detectable RNA cleavage.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.read more
Citations
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Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
The functions of animal microRNAs
TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
Journal ArticleDOI
Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
Lee P. Lim,Nelson C. Lau,Philip W. Garrett-engele,Andrew Grimson,Janell M. Schelter,John C. Castle,David P. Bartel,Peter S. Linsley,Jason M. Johnson +8 more
TL;DR: These results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts, and seem to downregulate a far greater number of targets than previously appreciated.
Journal ArticleDOI
Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
TL;DR: It is demonstrated that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5, an additional cellular cofactor required for miRNA biogenesis and function.
Journal ArticleDOI
Asymmetry in the assembly of the RNAi enzyme complex.
TL;DR: It is shown that the two strands of an siRNA duplex are not equally eligible for assembly into RISC, and it is suggested that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed.
References
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Andrew Fire,SiQun Xu,Mary K. Montgomery,Steven A. Kostas,Steven A. Kostas,Samuel E. Driver,Craig C. Mello +6 more
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The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
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Journal ArticleDOI
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TL;DR: Dicer is a member of the RNase III family of nucleases that specifically cleave double-stranded RNAs, and is evolutionarily conserved in worms, flies, plants, fungi and mammals, and has a distinctive structure, which includes a helicase domain and dualRNase III motifs.
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The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
Brenda J. Reinhart,Frank J. Slack,Frank J. Slack,Michael Basson,Amy E. Pasquinelli,Bettinger Jc,Ann E. Rougvie,H R Horvitz,Gary Ruvkun +8 more
TL;DR: It is shown that let-7 is a heterochronic switch gene that encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heteroch chronic genes lin-14, lin-28, Lin-41, lin -42 and daf-12, indicating that expression of these genes may be directly controlled by let- 7.