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

Area of Science:

• Molecular Biology
• Cell Biology
• RNA Biology

Background:

• Limited understanding of general nuclear transport mechanisms for nucleic acids like oligonucleotides (ONs), siRNAs, and miRNAs.
• Prior studies identified factors binding specific nucleic acid subsets, but a universal transport pathway remained elusive.

Purpose of the Study:

• To investigate the nuclear transport of ONs, siRNAs, and miRNAs.
• To identify the molecular machinery and conditions regulating this transport.

Main Methods:

• Induction of cellular stress.
• Biochemical analysis to identify protein complexes involved in nuclear transport.
• Assessment of nucleic acid (miRNA, siRNA, ON) localization and function within the nucleus under stress conditions.

Main Results:

• Nuclear transport of ONs, siRNAs, and miRNAs is responsive to cellular stress.
• Identification of a novel stress-induced response complex (SIRC) comprising Ago-1, Ago-2, YB1, CTCF, FUS, Smad1, Smad3, and Smad4.
• SIRC facilitates the nuclear import of endogenous miRNAs, siRNAs, and ONs.

Conclusions:

• Cellular stress activates a specific pathway for nuclear import of various nucleic acid types.
• The SIRC complex is a key mediator of this stress-induced nuclear transport.
• This mechanism enhances the efficiency of ON/siRNA-mediated splicing modulation and nuclear RNA targeting by endogenous miRNAs.