Asymmetry in the assembly of the RNAi enzyme complex

Dianne S. Schwarz, Gyorgy Hutvagner, Tingting Du, Zuoshang Xu, Neil Aronin, Phillip D. Zamore

    Research output: Contribution to journalArticlepeer-review

    2174 Citations (Scopus)


    A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5' ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest 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. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.
    Original languageEnglish
    Pages (from-to)199-208
    Number of pages10
    Issue number2
    Publication statusPublished - 2003


    • RNA interference
    • Antisense metabolism
    • Messenger metabolism
    • Small interfering metabolism
    • Untranslated metabolism
    • RNA-induced silencing complex metabolism
    • Double-stranded RNA


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