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Cleavage of the Star Strand Facilitates Assembly of Some MicroRNAs into Ago2-containing Silencing Complexes in Mammals  

Shin, Chanseok (The Whitehead Institute for Biomedical Research)
Abstract
In animals, microRNAs (miRNAs) and small interfering RNAs (siRNAs) repress expression of protein coding genes by assembling distinct RNA-induced silencing complexes (RISCs). It has previously been shown that passenger-strand cleavage is the predominant mechanism when siRNA duplexes are loaded into Argonaute2 (Ago2)-containing RISC, while an unwinding bypass mechanism is favored for miRNA duplexes with mismatches. Here I present experimental data indicating that some mammalian miRNAs are assembled into Ago2-containing RISC by cleaving their corresponding miRNA star strands. This phenomenon may depend on the secondary structure near the scissile phosphate of the miRNA duplex. In addition, I show that ATP is not required for star-strand cleavage in this process. Taken together, the data here provide insight into the miRNA-loading mechanisms in mammals.
Keywords
Argonaute; microRNA; miRNA star-strand cleavage; passenger-strand cleavage; RISC;
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