Staufen from embryo polarity to cellular stress and neurodegeneration

Boccaccio, Graciela Lidia

doi:10.2741/s277

Cited by 15 publications

(1 citation statement)

References 119 publications

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“…The third dsRNA binding domain (dsRBD3) of Staufen1 interacts specifically with the zinc fingers of the NC domain of Gag in an RNA-independent manner (Chatel-Chaix et al 2008). This interaction results in the formation of high molecular weight, detergent insoluble, Staufen1-HIV-1-dependent RNPs (SHRNPs), also containing Gag, Upf1, and the vRNA, and many other viral and cellular proteins (Mallardo et al 2003;Chatel-Chaix et al 2004, 2007Abrahamyan et al 2010;Milev et al 2012;Tosar et al 2012). In the context of SHRNPs, Staufen1 likely interacts with the NC domain of Gag to enhance Gag assembly and vRNA packaging (Abrahamyan et al 2010;Milev et al 2010).…”

Section: Introductionmentioning

confidence: 99%

HIV-1 requires Staufen1 to dissociate stress granules and to produce infectious viral particles

Rao

Hassine

Monette

et al. 2019

RNA

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The human immunodeficiency virus type 1 (HIV-1) genomic RNA (vRNA) has two major fates during viral replication: to serve as the template for the major structural and enzymatic proteins, or to be encapsidated and packaged into assembling virions to serve as the genomic vRNA in budding viruses. The dynamic balance between vRNA translation and encapsidation is mediated by numerous host proteins, including Staufen1. During HIV-1 infection, HIV-1 recruits Staufen1 to assemble a distinct ribonucleoprotein complex promoting vRNA encapsidation and viral assembly. Staufen1 also rescues vRNA translation and gene expression during conditions of cellular stress. In this work, we utilized novel Staufen1 −/− gene-edited cells to further characterize the contribution of Staufen1 in HIV-1 replication. We observed a marked deficiency in the ability of HIV-1 to dissociate stress granules (SGs) in Staufen1-deficient cells and remarkably, the vRNA repositioned to SGs. These phenotypes were rescued by Staufen1 expression in trans or in cis, but not by a dsRBD-binding mutant, Staufen1F135A. The mistrafficking of the vRNA in these Staufen1 −/− cells was also accompanied by a dramatic decrease in viral production and infectivity. This work provides novel insight into the mechanisms by which HIV-1 uses Staufen1 to ensure optimal vRNA translation and trafficking, supporting an integral role for Staufen1 in the HIV-1 life cycle, positioning it as an attractive target for next-generation antiretroviral agents.

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Section: Introductionmentioning

confidence: 99%

HIV-1 requires Staufen1 to dissociate stress granules and to produce infectious viral particles

Rao

Hassine

Monette

et al. 2019

RNA

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Synaptic control of local translation: the plot thickens with new characters

Thomas

Pascual

Maschi

et al. 2013

Cell. Mol. Life Sci.

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The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

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