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Jun Li, Cancan Chen, Xiancai Ma, Guannan Geng, Bingfeng Liu, Yijun Zhang, Shaoyang Zhang, Fudi Zhong, Chao Liu, Yue Yin, Weiping Cai, Hui Zhang
Long noncoding RNAs (lncRNAs) play multiple key regulatory roles in various cellular pathways. However, their functions in HIV-1 latent infection remain largely unknown. Here we show that a lncRNA named NRON, which is highly expressed in resting CD4(+) T lymphocytes, could be involved in HIV-1 latency by specifically inducing Tat protein degradation. Our results suggest that NRON lncRNA potently suppresses the viral transcription by decreasing the cellular abundance of viral transactivator protein Tat. NRON directly links Tat to the ubiquitin/proteasome components including CUL4B and PSMD11, thus facilitating Tat degradation...
2016: Nature Communications
Yool Lee, A Reum Jang, Lauren J Francey, Amita Sehgal, John B Hogenesch
Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells...
2015: ELife
Hasan Imam, Aalia Shahr Bano, Paresh Patel, Prasida Holla, Shahid Jameel
A majority of the human genome is transcribed into noncoding RNAs, of which the functions of long noncoding RNAs (lncRNAs) are poorly understood. Many host proteins and RNAs have been characterized for their roles in HIV/AIDS pathogenesis, but there is only one lncRNA, NEAT1, which is shown to affect the HIV-1 life cycle. We profiled 90 disease-related lncRNAs and found NRON (noncoding repressor of Nuclear Factor of Activated T cells [NFAT]) to be one of several lncRNAs whose expression was significantly altered following HIV-1 infection...
2015: Scientific Reports
Hsiao-Wei Tsao, Tzong-Shyuan Tai, William Tseng, Hui-Hsin Chang, Roland Grenningloh, Shi-Chuen Miaw, I-Cheng Ho
E26 transformation-specific sequence 1 (Ets-1), the prototype of the ETS family of transcription factors, is critical for the expression of IL-2 by murine Th cells; however, its mechanism of action is still unclear. Here we show that Ets-1 is also essential for optimal production of IL-2 by primary human Th cells. Although Ets-1 negatively regulates the expression of Blimp1, a known suppressor of IL-2 expression, ablation of B lymphocyte-induced maturation protein 1 (Blimp1) does not rescue the expression of IL-2 by Ets-1-deficient Th cells...
September 24, 2013: Proceedings of the National Academy of Sciences of the United States of America
Yu-ye Tang, Li-ke Wo, Hui Chai
OBJECTIVE: To determine the effects of noncoding repressor of NFAT (NRON) overexpression or silencing on human umbilical vein endothelial cells (HUVECs) functions. METHODS: Stable HUVECs cell lines with NRON overexpression and short hairpin RNA (shRNA) interference were obtained. HUVECs, the empty vector pBABE-cell line and the empty vector pSuper-cell line served as controls. Cell proliferations of these cell lines were tested using MTS method, tube formation capacity and migration function were also examined...
March 2013: Zhonghua Xin Xue Guan Bing za Zhi
Puja Vora, Dermot P B McGovern
Inflammatory bowel disease encompasses two chronic, complex relapsing diseases believed to be caused by an excessive and poorly controlled immune response to the intestinal microbiota. The advent of genome-wide association scans has allowed for rapid identification of multiple susceptibility genes for Crohn's disease and ulcerative colitis. A locus containing LRRK2 and MUC19 is a confirmed Crohn's disease susceptibility locus. This genetic association precipitates an important functional study in which Liu et al...
March 2012: Expert Review of Clinical Immunology
Zhihua Liu, Jinwoo Lee, Scott Krummey, Wei Lu, Huaibin Cai, Michael J Lenardo
Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally...
November 2011: Nature Immunology
Sonia Sharma, Gregory M Findlay, Hozefa S Bandukwala, Shalini Oberdoerffer, Beate Baust, Zhigang Li, Valentina Schmidt, Patrick G Hogan, David B Sacks, Anjana Rao
Nuclear factor of activated T cells (NFAT) proteins are Ca(2+)-regulated transcription factors that control gene expression in many cell types. NFAT proteins are heavily phosphorylated and reside in the cytoplasm of resting cells; when cells are stimulated by a rise in intracellular Ca(2+), NFAT proteins are dephosphorylated by the Ca(2+)/calmodulin-dependent phosphatase calcineurin and translocate to the nucleus to activate target gene expression. Here we show that phosphorylated NFAT1 is present in a large cytoplasmic RNA-protein scaffold complex that contains a long intergenic noncoding RNA (lincRNA), NRON [noncoding (RNA) repressor of NFAT]; a scaffold protein, IQ motif containing GTPase activating protein (IQGAP); and three NFAT kinases, casein kinase 1, glycogen synthase kinase 3, and dual specificity tyrosine phosphorylation regulated kinase...
July 12, 2011: Proceedings of the National Academy of Sciences of the United States of America
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