scholarly journals The Human Fragile X Mental Retardation Protein Inhibits the Elongation Step of Translation through Its RGG and C-Terminal Domains

Biochemistry ◽  
2020 ◽  
Vol 59 (40) ◽  
pp. 3813-3822
Author(s):  
Youssi M. Athar ◽  
Simpson Joseph
Keyword(s):  
Mental Retardation ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Elongation Step ◽  
Terminal Domains

scholarly journals The Human Fragile X Mental Retardation Protein Inhibits the Elongation Step of Translation through its RGG and C-terminal domains

2020 ◽  
Author(s):  
Youssi M. Athar ◽  
Simpson Joseph
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
Mrna Translation ◽  
Translation Inhibition ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Elongation Step ◽  
Independent Translation

AbstractFragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates the translation of numerous mRNAs in neurons. The precise mechanism of translational regulation by FMRP is unknown. Some studies have indicated that FMRP inhibits the initiation step of translation, whereas other studies have indicated that the elongation step of translation is inhibited by FMRP. To determine whether FMRP inhibits the initiation or the elongation step of protein synthesis, we investigated m7G-cap-dependent and IRES-driven, cap-independent translation of several reporter mRNAs in vitro. Our results show that FMRP inhibits both m7G-cap-dependent and cap-independent translation to similar degrees, indicating that the elongation step of translation is inhibited by FMRP. Additionally, we dissected the RNA-binding domains of hFMRP to determine the essential domains for inhibiting translation. We show that the RGG domain, together with the C-terminal domain (CTD), is sufficient to inhibit translation while the KH domains do not inhibit mRNA translation. However, the region between the RGG domain and the KH2 domain may contribute as NT-hFMRP shows more potent inhibition than the RGG-CTD tail alone. Interestingly, we see a correlation between ribosome binding and translation inhibition, suggesting the RGG-CTD tail of hFMRP may anchor FMRP to the ribosome during translation inhibition.

scholarly journals DrosophilaTorsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Phuong Nguyen ◽  
Jong Bok Seo ◽  
Hyo-Min Ahn ◽  
Young Ho Koh
Keyword(s):  
Mental Retardation ◽  
Protein Complexes ◽  
Fragile X ◽  
Stress Sensitivity ◽  
Altered Expression ◽  
Fragile X Mental Retardation ◽  
Evolutionarily Conserved ◽  
Mental Retardation Protein ◽  
Synaptic Boutons

We investigated unknownin vivofunctions of Torsin by usingDrosophilaas a model. Downregulation ofDrosophilaTorsin (DTor) by DTor-specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported inDrosophilaFragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies ofdfmrpnull mutants anddfmrpmutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved.

scholarly journals The FMRP/GRK4mRNA interaction uncovers a new mode of binding of the Fragile X mental retardation protein in cerebellum

2015 ◽  
Vol 43 (17) ◽  
pp. 8540-8550 ◽  
Author(s):  
Thomas Maurin ◽  
Mireille Melko ◽  
Sabiha Abekhoukh ◽  
Olfa Khalfallah ◽  
Laetitia Davidovic ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein
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