Abstract
Once loaded onto Argonaute proteins, microRNAs form a silencing complex called miRISC that targets mostly the 3’UTR of mRNAs to silence their translation. How microRNAs are transported to and from their target mRNA remains poorly characterized. While some reports linked intracellular trafficking to microRNA activity, it is still unclear how these pathways coordinate for proper microRNA-mediated gene silencing and turnover. Through a forward genetic screen using Caenorhabditis elegans, we identified the RabGAP tbc-11 as an important factor for the microRNA pathway. We show that TBC-11 acts mainly through the small GTPase RAB-6 and that its regulation is required for microRNA function. The absence of functional TBC-11 increases the pool of microRNA-unloaded Argonaute ALG-1 that is likely associated to endomembranes. Furthermore, in this condition, this pool of Argonaute accumulates in a perinuclear region and forms a high molecular weight complex. Altogether, our data suggest that the alteration of TBC-11 generates a fraction of ALG-1 that cannot bind to target mRNAs, leading to defective gene repression. Our results establish the importance of intracellular trafficking for microRNA function and demonstrate the involvement of a small GTPase and its GAP in proper Argonaute localization in vivo.
Highlights
MicroRNAs are endogenous small RNAs that regulate a wide variety of biological functions through post-transcriptional gene silencing
While research on microRNAs has brought a lot of interest over the last years, it is still unclear what modulators affect the activity of the microRNA-Induced Silencing Complex (miRISC)
Our study identified proteins implicated in intracellular trafficking as important factors for miRISC function
Summary
MicroRNAs (miRNA) are endogenous small RNAs that regulate a wide variety of biological functions through post-transcriptional gene silencing. With the help of effector proteins such as GW182, the miRISC can induce different molecular mechanisms leading to the abrogation of protein expression from the targeted mRNA such as translational repression, deadenylation, decapping or decay. While it is still unclear which one of these repression mechanisms occurs first, some studies suggest that the choice of favoured mechanism may be context specific (for example, see [5,6,7,8,9,10,11]). The composition and repression mechanism of miRISC vary between cell types and stages of development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
