hnRNP A2 and hnRNP L Bind the 3′UTR of Glucose Transporter 1 mRNA and Exist as a Complex in Vivo

Hamilton, Byron B.; Nichols, Ralph C.; Tsukamoto, Haruhisa; Boado, Rubén J.; Pardridge, William M.; Rigby, William F.C.

doi:10.1006/bbrc.1999.1040

Cited by 85 publications

(77 citation statements)

References 28 publications

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“…S2), some of them have already been shown to regulate VEGFA mRNA fate, including polypyrimidine tract-binding protein 1 isoform b (PTB) and TIA-1-related protein (TIAR)], 42 and others have been also tested under hypoxia conditions [e.g., heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), hnRNP A2/B1, and hnRNP L]. [43][44][45] To our knowledge, the impact on VEGFA regulation by some of the RBPs identified in our screen [for example, GTP-binding nuclear protein Ran (Fig. S2)] has never been studied.…”

Section: Discussionmentioning

confidence: 99%

Induction of VEGFA mRNA translation by CoCl₂ mediated by HuR

et al. 2015

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These authors equally contributed to the work.Keywords: biotin pulldown, mass spectrometry, post-transcriptional gene regulation, polysome profiling, ribonucleoprotein complex, RNA-binding proteins Vascular endothelial growth factor (VEGF) A is a master regulator of neovascularization and angiogenesis. VEGFA is potently induced by hypoxia and by pathological conditions including diabetic retinopathy and tumorigenesis. Finetuning of VEGFA expression by different stimuli is important for maintaining tissue vascularization and organ homeostasis. Here, we tested the effect of the hypoxia mimetic cobalt chloride (CoCl 2 ) on VEGFA expression in human cervical carcinoma HeLa cells. We found that CoCl 2 increased the levels of VEGFA mRNA and VEGFA protein without affecting VEGFA mRNA stability. Biotin pulldown analysis to capture the RNA-binding proteins (RBPs) bound to VEGFA mRNA followed by mass spectrometry analysis revealed that the RBP HuR [human antigen R, a member of the embryonic lethal abnormal vision (ELAV) family of proteins], interacts with VEGFA mRNA. VEGFA mRNA-tagging experiments showed that exposure to CoCl 2 increases the interaction of HuR with VEGFA mRNA and promoted the colocalization of HuR and the distal part of the VEGFA 3 0 -untranslated region (UTR) in the cytoplasm. We propose that under hypoxia-like conditions, HuR enhances VEGFA mRNA translation.

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Section: Discussionmentioning

confidence: 99%

Induction of VEGFA mRNA translation by CoCl₂ mediated by HuR

et al. 2015

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“…Thus, under conditions of chronic cellular stress translocation of A2/RA33 to the cytoplasm seems to occur in which this protein may exert a hitherto unknown function. A2/RA33 is a shuttling protein involved in transport of certain mRNAs and possibly also in regulation of their translation as suggested for myelin basic protein or glucose transporter 1 (66,67). Like other shuttling proteins, A2/RA33 is known to undergo posttranslational modifications such as phosphorylation or methylation (68,69).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Autoreactive T Cells to the Autoantigens Heterogeneous Nuclear Ribonucleoprotein A2 (RA33) and Filaggrin in Patients with Rheumatoid Arthritis

Fritsch¹,

Eselböck²,

Skriner³

et al. 2002

The Journal of Immunology

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The role of autoimmune reactions in the pathogenesis of rheumatoid arthritis (RA) is poorly understood. To address this issue we have investigated the spontaneous T cell response to two well-characterized humoral autoantigens in RA patients and controls: 1) the heterogeneous nuclear ribonucleoprotein A2, i.e., the RA33 Ag (A2/RA33), and 2) filaggrin in unmodified and citrullinated forms. In stimulation assays A2/RA33 induced proliferative responses in PBMC of almost 60% of the RA patients but in only 20% of the controls (patients with osteoarthritis or psoriatic arthritis and healthy individuals), with substantially stronger responses in RA patients (p < 0.00002). Furthermore, synovial T cells of seven RA patients investigated were also clearly responsive. In contrast, responses to filaggrin were rarely observed and did not differ between RA patients and controls. Analysis of A2/RA33-induced cytokine secretion revealed high IFN-γ and low IL-4 production in both RA and control PBMC, whereas IL-2 production was mainly observed in RA PBMC (p < 0.03). Moreover, A2/RA33-specific T cell clones from RA patients showed a strong Th1 phenotype and secreted higher amounts of IFN-γ than Th1 clones from controls (p < 0.04). Inhibition experiments performed with mAbs against MHC class II molecules showed A2/RA33-induced T cell responses to be largely HLA-DR restricted. Finally, immunohistochemical analyses revealed pronounced overexpression of A2/RA33 in synovial tissue of RA patients. Taken together, the presence of autoreactive Th1-like cells in RA patients in conjunction with synovial overexpression of A2/RA33 may indicate potential involvement of this autoantigen in the pathogenesis of RA.

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“…The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is implicated in RNA processing, RNA transport, and translation regulation (Dreyfuss et al, 1993;Siomi and Dreyfuss, 1995;Hamilton et al, 1999;Kwon et al, 1999). HnRNP A2 binds to a specific cis-acting element, hnRNP A2 response element (A2RE), found in several dendritically localized mRNAs Munro et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The Microtubule-associated Protein Tumor Overexpressed Gene Binds to the RNA Trafficking Protein Heterogeneous Nuclear Ribonucleoprotein A2

Kosturko

Maggipinto

D'Sa

et al. 2005

MBoC

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In neural cells, such as oligodendrocytes and neurons, transport of certain RNAs along microtubules is mediated by the cis-acting heterogeneous nuclear ribonucleoprotein A2 response element (A2RE) trafficking element and the cognate trans-acting heterogeneous nuclear ribonucleoprotein (hnRNP) A2 trafficking factor. Using a yeast two-hybrid screen, we have identified a microtubule-associated protein, tumor overexpressed gene (TOG)2, as an hnRNP A2 binding partner. The C-terminal third of TOG2 is sufficient for hnRNP A2 binding. TOG2, the large protein isoform of TOG, is the only isoform detected in oligodendrocytes in culture. TOG coimmunoprecipitates with hnRNP A2 present in the cytoskeleton (CSK) fraction of neural cells, and both coprecipitate with microtubule stabilized pellets. Staining with anti-TOG reveals puncta that are localized in proximity to microtubules, often at the plus ends. TOG is colocalized with hnRNP A2 and A2RE-mRNA in trafficking granules that remain associated with CSK-insoluble tissue. These data suggest that TOG mediates the association of hnRNP A2-positive granules with microtubules during transport and/or localization. INTRODUCTIONThe heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is implicated in RNA processing, RNA transport, and translation regulation (Dreyfuss et al., 1993;Siomi and Dreyfuss, 1995;Hamilton et al., 1999;Kwon et al., 1999). HnRNP A2 binds to a specific cis-acting element, hnRNP A2 response element (A2RE), found in several dendritically localized mRNAs Munro et al., 1999). This interaction is necessary for transport of A2RE-mRNAs to the periphery of neural cells (Munro et al., 1999;Shan et al., 2003).A2RE-mRNAs, hnRNP A2, and other components form complexes that look by light microscopy like granules that are transported to the cell periphery by a microtubule-and kinesin-based mechanism. In cultured oligodendrocytes and neurons, granules containing A2RE-mRNAs and hnRNP A2 are associated with the cytoskeleton (CSK) . HnRNP A2 and some A2RE-mRNAs copurify with the CSK from rat brain (Hoek et al., 1998;Boccaccio et al., 1999).To identify molecular partners of hnRNP A2, we performed yeast two-hybrid analysis. One of the components identified is the tumor overexpressed gene (TOG) protein, a microtubule-associated protein (MAP) ubiquitously expressed in human tissues. TOG is a single copy gene that generates two mRNA splice variants (Nagase et al., 1995;Charrasse et al., 1998) encoding proteins that differ by a 60-aa insert near the C terminus. In dividing cells, TOG localizes with centrosome and spindle microtubules and may be necessary for microtubule rearrangements and spindle assembly (Charrasse et al., 1998;Lee et al., 2001). Orthologues of colonic and hepatic tumor overexpressed gene (ch-TOG) (Homo sapiens), Dis1p, Stu2p, XMAP215, ZYG-9, and mini spindles, in fission yeast, budding yeast, Xenopus laevis, Caenorhabditis elegans, and Drosophila melanogaster, respectively, have similar functions. TOG and its orthologues all contain multiple HEAT repeats that may serv...

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hnRNP A2 and hnRNP L Bind the 3′UTR of Glucose Transporter 1 mRNA and Exist as a Complex in Vivo

Cited by 85 publications

References 28 publications

Induction of VEGFA mRNA translation by CoCl₂ mediated by HuR

Induction of VEGFA mRNA translation by CoCl₂ mediated by HuR

Characterization of Autoreactive T Cells to the Autoantigens Heterogeneous Nuclear Ribonucleoprotein A2 (RA33) and Filaggrin in Patients with Rheumatoid Arthritis

The Microtubule-associated Protein Tumor Overexpressed Gene Binds to the RNA Trafficking Protein Heterogeneous Nuclear Ribonucleoprotein A2

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hnRNP A2 and hnRNP L Bind the 3′UTR of Glucose Transporter 1 mRNA and Exist as a Complex in Vivo

Cited by 85 publications

References 28 publications

Induction of VEGFA mRNA translation by CoCl2 mediated by HuR

Induction of VEGFA mRNA translation by CoCl2 mediated by HuR

Characterization of Autoreactive T Cells to the Autoantigens Heterogeneous Nuclear Ribonucleoprotein A2 (RA33) and Filaggrin in Patients with Rheumatoid Arthritis

The Microtubule-associated Protein Tumor Overexpressed Gene Binds to the RNA Trafficking Protein Heterogeneous Nuclear Ribonucleoprotein A2

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Induction of VEGFA mRNA translation by CoCl₂ mediated by HuR

Induction of VEGFA mRNA translation by CoCl₂ mediated by HuR