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  • The FMRP-MOV10 complex: a translational regulatory switch modulated by G-Quadruplexes.

The FMRP-MOV10 complex: a translational regulatory switch modulated by G-Quadruplexes.

Nucleic acids research (2019-11-20)
Phillip J Kenny, Miri Kim, Geena Skariah, Joshua Nielsen, Monica C Lannom, Stephanie Ceman
要旨

The Fragile X Mental Retardation Protein (FMRP) is an RNA binding protein that regulates translation and is required for normal cognition. FMRP upregulates and downregulates the activity of microRNA (miRNA)-mediated silencing in the 3' UTR of a subset of mRNAs through its interaction with RNA helicase Moloney leukemia virus 10 (MOV10). This bi-functional role is modulated through RNA secondary structures known as G-Quadruplexes. We elucidated the mechanism of FMRP's role in suppressing Argonaute (AGO) family members' association with mRNAs by mapping the interacting domains of FMRP, MOV10 and AGO and then showed that the RGG box of FMRP protects a subset of co-bound mRNAs from AGO association. The N-terminus of MOV10 is required for this protection: its over-expression leads to increased levels of the endogenous proteins encoded by this co-bound subset of mRNAs. The N-terminus of MOV10 also leads to increased RGG box-dependent binding to the SC1 RNA G-Quadruplex and is required for outgrowth of neurites. Lastly, we showed that FMRP has a global role in miRNA-mediated translational regulation by recruiting AGO2 to a large subset of RNAs in mouse brain.

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Sigma-Aldrich
ポリエチレンイミン、分岐, average Mw ~25,000 by LS, average Mn ~10,000 by GPC, branched
Millipore
抗c-Myc抗体-アガロース アフィニティーゲル ウサギ宿主抗体, affinity isolated antibody
Sigma-Aldrich
抗pan Ago抗体、クローン2A8, clone 2A8, from mouse