2017
DOI: 10.1016/j.celrep.2017.06.027
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Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins

Abstract: SummaryAs core components of the microRNA-induced silencing complex (miRISC), Argonaute (AGO) proteins interact with TNRC6 proteins, recruiting other effectors of translational repression/mRNA destabilization. Here, we show that LIMD1 coordinates the assembly of an AGO-TNRC6 containing miRISC complex by binding both proteins simultaneously at distinct interfaces. Phosphorylation of AGO2 at Ser 387 by Akt3 induces LIMD1 binding, which in turn enables AGO2 to interact with TNRC6A and downstream effector DDX6. Co… Show more

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Cited by 57 publications
(64 citation statements)
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“…Previous reports suggest the Ago2‐GW182 interaction is regulated in HeLa cells by phosphorylation of Ago2 at S387 by the kinase Akt (Horman et al , 2013; Bridge et al , 2017). We therefore hypothesised that the NMDAR‐stimulated increase in binding would be mediated by a similar mechanism.…”
Section: Resultsmentioning
confidence: 98%
See 1 more Smart Citation
“…Previous reports suggest the Ago2‐GW182 interaction is regulated in HeLa cells by phosphorylation of Ago2 at S387 by the kinase Akt (Horman et al , 2013; Bridge et al , 2017). We therefore hypothesised that the NMDAR‐stimulated increase in binding would be mediated by a similar mechanism.…”
Section: Resultsmentioning
confidence: 98%
“…While S387 is situated between the PAZ and MID domains of Ago2, GW182 associates with the PIWI domain towards the C‐terminus of Ago2 (Pfaff et al , 2013), suggesting that phosphorylated S387 is unlikely to contribute to the GW182 binding site directly. A recent study provides an explanation for this by demonstrating that the LIM‐domain protein LIMD1 binds both GW182 and S387‐phosphorylated Ago2 in HeLa cells and stabilises the interaction between Ago2 and GW182 in response to Ago2 phosphorylation (Bridge et al , 2017). Interestingly, this report further suggests that DDX6 is also recruited to Ago2 by S387 phosphorylation, presumably by interacting with GW182 following LIMD1 binding.…”
Section: Discussionmentioning
confidence: 99%
“…This mode of action will ultimately lead to translation inhibition of Ago1/2 targets (James et al, 2010). A more recent study has determined that the LIM domains of LIMD1 are the interaction surface with TNRC6A (Bridge et al, 2017). Moreover, LIMD1 bridges AGO2 to TNRC6A/miRISC (Bridge et al, 2017).…”
Section: A Parallel Between Gtsf-1 In Animals and Stc1 In Fission Yeastmentioning
confidence: 99%
“…A more recent study has determined that the LIM domains of LIMD1 are the interaction surface with TNRC6A (Bridge et al, 2017). Moreover, LIMD1 bridges AGO2 to TNRC6A/miRISC (Bridge et al, 2017).…”
Section: A Parallel Between Gtsf-1 In Animals and Stc1 In Fission Yeastmentioning
confidence: 99%
“…Interestingly, AGO2‐RV‐NSP1 association was found to be unperturbed in the presence of both single‐stranded RNA‐specific RNase I and double‐stranded RNA‐specific RNase III (Figure b), excluding the possibility of viral RNA scaffold to have a mediating role. AGO2 activity has been reported to be regulated by phosphorylation (Bridge et al, ; Horman et al, ). Phosphorylation of RV‐OSU‐NSP1 by caesin kinase II has also recently been shown to be a prerequisite for NSP1‐βTrCP association (Davis et al, ).…”
Section: Resultsmentioning
confidence: 99%