MicroRNA (miRNA)‐guided mRNA repression, mediated by the miRNA‐induced silencing complex (miRISC), is an important component of post‐transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). Nup358 depletion disrupts P bodies and concomitantly impairs the miRNA pathway. Furthermore, Nup358 interacts with AGO and GW182 proteins and promotes the association of target mRNA with miRISC. A well‐characterized SUMO‐interacting motif (SIM) in Nup358 is sufficient for Nup358 to directly bind to AGO proteins. Moreover, AGO and PIWI proteins interact with SIMs derived from other SUMO‐binding proteins. Our study indicates that Nup358–AGO interaction is important for miRNA‐mediated gene silencing and identifies SIM as a new interacting motif for the AGO family of proteins. The findings also support a model wherein the coupling of miRISC with the target mRNA could occur at AL, specialized domains within the ER, and at the nuclear envelope.
The nucleoporin Nup358 promotes the association of target mRNA with miRISC possibly at specialized ER domains and at the nuclear envelope. The study also identifies SIM as a new interacting motif for AGO family proteins.
Nup358 depletion disrupts P body formation and impairs the coupling of target mRNA with miRISC.
Nup358 interacts with AGO proteins through its SUMO‐interacting motifs (SIMs), and SIM is identified as a new binding motif for AGO family proteins.
The association of target mRNA with miRISC possibly occurs at Nup358‐positive structures on the ER called annulate lamellae and at the nuclear envelope.
EMBO Reports (2017) 18: 241–263
- Received March 15, 2016.
- Revision received November 13, 2016.
- Accepted November 24, 2016.
- © 2016 The Authors
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