A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus

Although some information is available for specific subsets of miRNAs and several factors have been shown to bind oligonucleotides (ONs), no general transport mechanism for these molecules has been identified to date. In this work, we demonstrate that the nuclear transport of ONs, siRNAs, and miRNAs responds to cellular stress. Furthermore, we have identified a stress-induced response complex (SIRC), which includes Ago-1 and Ago-2 in addition to the transcription and splicing regulators YB1, CTCF, FUS, Smad1, Smad3, and Smad4. The SIRC transports endogenous miRNAs, siRNAs, and ONs to the nucleus. We show that cellular stress can significantly increase ON- or siRNA-directed splicing switch events and endogenous miRNA targeting of nuclear RNAs.