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)
  • Received : 2008.07.31
  • Accepted : 2008.08.22
  • Published : 2008.09.30

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

Acknowledgement

Supported by : Damon Runyon Cancer Research Foundation

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