Unwinding the roles of RNA helicase MOV10.

MOV10 is an RNA helicase that associates with the RNA-induced silencing complex component Argonaute (AGO), likely resolving RNA secondary structures. MOV10 also binds the Fragile X mental retardation protein to block AGO2 binding at some sites and associates with UPF1, a principal component of the nonsense-mediated RNA decay pathway. MOV10 is widely expressed and has a key role in the cellular response to viral infection and in suppressing retrotransposition.

Translational control in aging and neurodegeneration.

Protein metabolism plays central roles in age-related decline and neurodegeneration. While a large body of research has explored age-related changes in protein degradation, alterations in the efficiency and fidelity of protein synthesis with aging are less well understood. Age-associated changes occur in both the protein synthetic machinery (ribosomal proteins and rRNA) and within regulatory factors controlling translation.

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

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.

Neuropathology of RAN translation proteins in fragile X-associated tremor/ataxia syndrome.

CGG repeat expansions in FMR1 cause the neurodegenerative disorder Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Ubiquitinated neuronal intranuclear inclusions (NIIs) are the neuropathological hallmark of FXTAS. Both sense strand derived CGG repeats and antisense strand derived CCG repeats support non-AUG initiated (RAN) translation of homopolymeric proteins in potentially 6 different reading frames.

Targeted Reactivation of Transcription in Fragile X Syndrome Embryonic Stem Cells.

Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism. It results from expansion of a CGG nucleotide repeat in the 5' untranslated region (UTR) of . Large expansions elicit repeat and promoter hyper-methylation, heterochromatin formation, transcriptional silencing and loss of the Fragile X protein, FMRP.

RNA helicase Mov10 is essential for gastrulation and central nervous system development.

Background: Mov10 is an RNA helicase that modulates access of Argonaute 2 to microRNA recognition elements in mRNAs. We examined the role of Mov10 in Xenopus laevis development and show a critical role for Mov10 in gastrulation and in the development of the central nervous system (CNS).

Results: Knockdown of maternal Mov10 in Xenopus embryos using a translation blocking morpholino led to defects in gastrulation and the development of notochord and paraxial mesoderm, and a failure to neurulate.

Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain.

Background: Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse.

MOV10 and FMRP regulate AGO2 association with microRNA recognition elements.

The fragile X mental retardation protein FMRP regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway, and we show here that it associates with the RNA helicase MOV10, also associated with the microRNA pathway. FMRP associates with MOV10 directly and in an RNA-dependent manner and facilitates MOV10's association with RNAs in brain and cells, suggesting a cooperative interaction.

2'-O-methylation of the wobble residue of elongator pre-tRNA(Met) in Haloferax volcanii is guided by a box C/D RNA containing unique features.

The wobble residue C34 of Haloferax volcanii elongator tRNA(Met) is 2'-O-methylated. Neither a protein enzyme nor a guide RNA for this modification has been described. In this study, we show that this methylation is guided by a box C/D RNA targeting the intron-containing precursor of the tRNA.

Small ubiquitin-related modifier ligase activity of Mms21 is required for maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in Saccharomyces cerevisiae.

The SUMO ligase activity of Mms21/Nse2, a conserved member of the Smc5/6 complex, is required for resisting extrinsically induced genotoxic stress. We report that the Mms21 SUMO ligase activity is also required during the unchallenged mitotic cell cycle in Saccharomyces cerevisiae. SUMO ligase-defective cells were slow growing and spontaneously incurred DNA damage.

Box C/D RNA-guided 2'-O methylations and the intron of tRNATrp are not essential for the viability of Haloferax volcanii.

Deleting the box C/D RNA-containing intron in the Haloferax volcanii tRNATrp gene abolishes RNA-guided 2'-O methylations of C34 and U39 residues of tRNATrp. However, this deletion does not affect growth under standard conditions.