共查询到20条相似文献,搜索用时 15 毫秒
1.
Testoni B Völlenkle C Guerrieri F Gerbal-Chaloin S Blandino G Levrero M 《The Journal of biological chemistry》2011,286(23):20217-20227
2.
3.
Xu Zhao Ying Yang Bao-Fa Sun Yue Shi Xin Yang Wen Xiao Ya-Juan Hao Xiao-Li Ping Yu-Sheng Chen Wen-Jia Wang Kang-Xuan Jin Xing Wang Chun-Min Huang Yu Fu Xiao-Meng Ge Shu-Hui Song Hyun Seok Jeong Hiroyuki Yanagisawa Yamei Niu Gui-Fang Jia Wei Wu Wei-Min Tong Akimitsu Okamoto Chuan He Jannie M Rendtlew Danielsen Xiu-Jie Wang Yun-Gui Yang 《Cell research》2014,24(12):1403-1419
4.
Du Z Wei L Murti A Pfeffer SR Fan M Yang CH Pfeffer LM 《Journal of cellular biochemistry》2007,102(5):1087-1094
5.
6.
7.
8.
N~6 -methyl-adenosine (m ~6A) in RNA: An Old Modification with A Novel Epigenetic Function 总被引:1,自引:0,他引:1
Yamei Niu Xu Zhao Yong-Sheng Wu Ming-Ming Li Xiu-Jie Wang Yun-Gui Yang 《基因组蛋白质组与生物信息学报(英文版)》2013,11(1):8-17
N6 -methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3’-untranslated region (3’-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an a-ketoglutarate (a-KG)-and Fe2+-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances. 相似文献
9.
Miaoge Xue Yuexiu Zhang Haitao Wang Elizabeth L. Kairis Mijia Lu Sadeem Ahmad Zayed Attia Olivia Harder Zijie Zhang Jiangbo Wei Phylip Chen Youling Gao Mark E. Peeples Amit Sharma Prosper Boyaka Chuan He Sun Hur Stefan Niewiesk Jianrong Li 《PLoS pathogens》2021,17(12)
Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in humans. A well-known challenge in the development of a live attenuated RSV vaccine is that interferon (IFN)-mediated antiviral responses are strongly suppressed by RSV nonstructural proteins which, in turn, dampens the subsequent adaptive immune responses. Here, we discovered a novel strategy to enhance innate and adaptive immunity to RSV infection. Specifically, we found that recombinant RSVs deficient in viral RNA N6-methyladenosine (m6A) and RSV grown in m6A methyltransferase (METTL3)-knockdown cells induce higher expression of RIG-I, bind more efficiently to RIG-I, and enhance RIG-I ubiquitination and IRF3 phosphorylation compared to wild-type virion RNA, leading to enhanced type I IFN production. Importantly, these m6A-deficient RSV mutants also induce a stronger IFN response in vivo, are significantly attenuated, induce higher neutralizing antibody and T cell immune responses in mice and provide complete protection against RSV challenge in cotton rats. Collectively, our results demonstrate that inhibition of RSV RNA m6A methylation enhances innate immune responses which in turn promote adaptive immunity. 相似文献
10.
11.
Human METTL16 is a N6‐methyladenosine (m6A) methyltransferase that targets pre‐mRNAs and various non‐coding RNAs
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Philipp Hackert Christof Lenz Henning Urlaub Claudia Höbartner Katherine E Sloan Markus T Bohnsack 《EMBO reports》2017,18(11):2004-2014
N6‐methyladenosine (m6A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m6A modifications are installed by the METTL3–METTL14 complex, others appear to be introduced independently, implying that additional human m6A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the putative human m6A “writer” protein METTL16 binds to the U6 snRNA and other ncRNAs as well as numerous lncRNAs and pre‐mRNAs. We demonstrate that METTL16 is responsible for N6‐methylation of A43 of the U6 snRNA and identify the early U6 biogenesis factors La, LARP7 and the methylphosphate capping enzyme MEPCE as METTL16 interaction partners. Interestingly, A43 lies within an essential ACAGAGA box of U6 that base pairs with 5′ splice sites of pre‐mRNAs during splicing, suggesting that METTL16‐mediated modification of this site plays an important role in splicing regulation. The identification of METTL16 as an active m6A methyltransferase in human cells expands our understanding of the mechanisms by which the m6A landscape is installed on cellular RNAs. 相似文献
12.
Macrophage polarization is the driving force of various inflammatory diseases, especially those involved in M1/M2 imbalance. N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in eukaryotes that affects multiple biological processes, including those involved developmental arrest and immune response. However, the role of m6A in macrophage polarization remains unclear. This study found that FTO silencing significantly suppressed both M1 and M2 polarization. FTO depletion decreased the phosphorylation levels of IKKα/β, IκBα and p65 in the NF-κB signaling pathway. The expression of STAT1 was downregulated in M1-polarized macrophages while the expression of STAT6 and PPAR-γ decreased in M2 polarization after FTO knockdown. The actinomycin D experiments showed that FTO knockdown accelerated mRNA decay of STAT1 and PPAR-γ. Furthermore, the stability and expression of STAT1 and PPAR-γ mRNAs increased when the m6A reader YTHDF2 was silenced. In conclusion, our results suggest that FTO knockdown inhibits the NF-κB signaling pathway and reduces the mRNA stability of STAT1 and PPAR-γ via YTHDF2 involvement, thereby impeding macrophage activation. These findings indicated a previously unrecognized link between FTO and macrophage polarization and might open new avenues for research into the molecular mechanisms of macrophage polarization-related diseases. 相似文献
13.
Mohamed Abou El Hassan Katherine Huang Manoja B. K. Eswara Zhaodong Xu Tao Yu Arthur Aubry Zuyao Ni Izzy Livne-bar Monika Sangwan Mohamad Ahmad Rod Bremner 《BMC molecular biology》2017,18(1):6
Background
STAT1 and IRF1 collaborate to induce interferon-γ (IFNγ) stimulated genes (ISGs), but the extent to which they act alone or together is unclear. The effect of single nucleotide polymorphisms (SNPs) on in vivo binding is also largely unknown.Results
We show that IRF1 binds at proximal or distant ISG sites twice as often as STAT1, increasing to sixfold at the MHC class I locus. STAT1 almost always bound with IRF1, while most IRF1 binding events were isolated. Dual binding sites at remote or proximal enhancers distinguished ISGs that were responsive to IFNγ versus cell-specific resistant ISGs, which showed fewer and mainly single binding events. Surprisingly, inducibility in one cell type predicted ISG-responsiveness in other cells. Several dbSNPs overlapped with STAT1 and IRF1 binding motifs, and we developed methodology to rapidly assess their effects. We show that in silico prediction of SNP effects accurately reflects altered binding both in vitro and in vivo.Conclusions
These data reveal broad cooperation between STAT1 and IRF1, explain cell type specific differences in ISG-responsiveness, and identify genetic variants that may participate in the pathogenesis of immune disorders.14.
15.
16.
Chien‐Chen Lai Kai‐Zen Lu Man‐Tzu Chiu Tsung‐Han Hsieh Lei Wan Cheng‐Wen Lin 《Proteomics》2013,13(23-24):3442-3456
Japanese encephalitis virus (JEV) nonstructural protein 5 (NS5) exhibits a Type I interferon (IFN) antagonistic function. This study characterizes Type I IFN antagonism mechanism of NS5 protein, using proteomic approach. In human neuroblastoma cells, NS5 expression would suppress IFNβ‐induced responses, for example, expression of IFN‐stimulated genes PKR and OAS as well as STAT1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS5 downregulating calreticulin, while upregulating cyclophilin A, HSP 60 and stress‐induced‐phosphoprotein 1. Gene silence of calreticulin raised intracellular Ca2+ levels while inhibiting nuclear translocalization of STAT1 and NFAT‐1 in response to IFNβ, thus, indicating calreticulin downregulation linked with Type I IFN antagonism of JEV NS5 via activation of Ca2+/calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5‐mediated inhibition of IFNβ‐induced responses, for example, IFN‐sensitive response element driven luciferase, STAT1‐dependent PKR mRNA expression, as well as phosphorylation and nuclear translocation of STAT1. Transfection with calcineurin (vs. control) siRNA enhanced nuclear translocalization of STAT1 and upregulated PKR expression in NS5‐expressing cells in response to IFNβ. Results prove Ca2+, calreticulin, and calcineurin involvement in STAT1‐mediated signaling as well as a key role of JEV NS5 in Type I IFN antagonism. This study offers insights into the molecular mechanism of Type I interferon antagonism by JEV NS5. 相似文献
17.
18.
19.