Heterotrimeric GAIT Complex Drives Transcript-Selective Translation Inhibition in Murine Macrophages

Arif, Abul; Chatterjee, Piyali; Moodt, Robyn A.; Fox, Paul L.

doi:10.1128/mcb.01168-12

Cited by 46 publications

(49 citation statements)

References 44 publications

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“…The results implicate orthologous hnRNPQ activities in human and avian cells integrate retroviral pre-mRNA splicing, processing, decay, and translation (Arif et al, 2012; Jurica et al, 2002; Weidensdorfer et al, 2009). Moreover, the co-isolation of ribosomal proteins, RNA synthetases and translation regulator proteins (DHX9, YY1, HuR) is reflective of the crosstalk between nuclear and cytoplasmic RNPs necessary for translation utilization of cellular mRNAs.…”

Section: Discussionmentioning

confidence: 73%

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Stake

Singh

et al. 2015

Virology

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Essential host cofactors in retrovirus replication bind cis-acting sequences in 5’untranslated region (UTR). Although host RBPs are crucial to all aspects of virus biology, elucidating their roles in replication remains a challenge to the field. Here RNA affinity-coupled-proteomics generated a comprehensive, unbiased inventory of human and avian RNA binding proteins (RBPs) co-isolating with 5’UTRs of HIV-1, spleen necrosis virus and Rous sarcoma virus. Applying stringent biochemical and statistical criteria, we identified 185 RBP; 122 were previously implicated in retrovirus biology and 63 are new to the 5’UTR proteome. RNA electrophoretic mobility assays investigated paralogs present in the common ancestor of vertebrates and one hnRNP was identified central node to the biological process-anchored networks of HIV-1, SNV, and RSV 5’ UTR-proteomes. This comprehensive view of the host constituents of retroviral RNPs is broadly applicable to investigation of viral replication and antiviral response in both human and avian cell lineages.

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Section: Discussionmentioning

confidence: 73%

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Stake

Singh

et al. 2015

Virology

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“…We first assessed whether IFN-γ signaling, the regulator of GAIT, influences IFN-γ expression in T cells. Neither culturing T cells with an exogenous concentration of IFN-γ that is known to induce GAIT in myeloid cells (Arif et al, 2012), nor the addition of neutralizing antibodies against IFN-γ, had any effect on IFN-γ expression by T cells (Figure S5B). We also immunoprecipitated GAPDH from glucose- and galactose-cultured cells and assessed the binding of other GAIT complex proteins to GAPDH by western blot.…”

Section: Resultsmentioning

confidence: 99%

Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

Chang

Curtis

Maggi

et al. 2013

Cell

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SUMMARY A “switch” from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete environment, remains incompletely understood. We show here that aerobic glycolysis is specifically required for effector function in T cells but that this pathway is not necessary for proliferation or survival. When activated T cells are provided with costimulation and growth factors but are blocked from engaging glycolysis, their ability to produce IFN-γ is markedly compromised. This defect is translational and is regulated by the binding of the glycolysis enzyme GAPDH to AU-rich elements within the 3′ UTR of IFN-γ mRNA. GAPDH, by engaging/disengaging glycolysis and through fluctuations in its expression, controls effector cytokine production. Thus, aerobic glycolysis is a metabolically regulated signaling mechanism needed to control cellular function.

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“…CDKAL1 has been described as a negative regulator of CDK5 through its homology to CDK5RAP1 [43], a well-characterized negative regulator of CDK5 [44] that functions through the inhibition of the CDK5 activator p35 [43], [45]. Recently, tRNA methyl transferase activites have been observed for both CDKAL1 and CDK5RAP1 [46], [47], suggesting additional complexities to the biology of CDK5, itself part of a complex that regulates selective mRNA transcripts through interactions with mRNA and tRNA synthetases [48], [49], further augmenting a large and diverse set of roles for CDK5 in multiple cell types [50].…”

Section: Resultsmentioning

confidence: 99%

RNAi Screening in Primary Human Hepatocytes of Genes Implicated in Genome-Wide Association Studies for Roles in Type 2 Diabetes Identifies Roles for CAMK1D and CDKAL1, among Others, in Hepatic Glucose Regulation

et al. 2013

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Genome-wide association (GWA) studies have described a large number of new candidate genes that contribute to of Type 2 Diabetes (T2D). In some cases, small clusters of genes are implicated, rather than a single gene, and in all cases, the genetic contribution is not defined through the effects on a specific organ, such as the pancreas or liver. There is a significant need to develop and use human cell-based models to examine the effects these genes may have on glucose regulation. We describe the development of a primary human hepatocyte model that adjusts glucose disposition according to hormonal signals. This model was used to determine whether candidate genes identified in GWA studies regulate hepatic glucose disposition through siRNAs corresponding to the list of identified genes. We find that several genes affect the storage of glucose as glycogen (glycolytic response) and/or affect the utilization of pyruvate, the critical step in gluconeogenesis. Of the genes that affect both of these processes, CAMK1D, TSPAN8 and KIF11 affect the localization of a mediator of both gluconeogenesis and glycolysis regulation, CRTC2, to the nucleus in response to glucagon. In addition, the gene CDKAL1 was observed to affect glycogen storage, and molecular experiments using mutant forms of CDK5, a putative target of CDKAL1, in HepG2 cells show that this is mediated by coordinate regulation of CDK5 and PKA on MEK, which ultimately regulates the phosphorylation of ribosomal protein S6, a critical step in the insulin signaling pathway.

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Heterotrimeric GAIT Complex Drives Transcript-Selective Translation Inhibition in Murine Macrophages

Cited by 46 publications

References 44 publications

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

RNAi Screening in Primary Human Hepatocytes of Genes Implicated in Genome-Wide Association Studies for Roles in Type 2 Diabetes Identifies Roles for CAMK1D and CDKAL1, among Others, in Hepatic Glucose Regulation

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