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Mol. Cells 2008; 26(3): 308-313

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

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

Chanseok Shin

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

Article

Research Article

Mol. Cells 2008; 26(3): 308-313

Published online September 30, 2008

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Chanseok Shin

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

Mol. Cells
Mar 31, 2023 Vol.46 No.3, pp. 131~189
COVER PICTURE
The physiologically important cytoprotective signaling in normal cells (background area in turquoise) mediated by NRF2 (blue chain) is often hijacked by cancer cells (red ball) in the tumor microenvironment (yellow area). However, the differential roles of NRF2 throughout the multistage carcinogenesis remains largely unresolved (white-colored overlapping misty areas).

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