In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively...In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively known as the ribonome, are tightly controlled and carried out by a plethora of trans-acting RNA-binding proteins （RBPs） that bind to specific cis elements throughout the RNA sequence. Within the nervous system, the role of RBPs in brain function turns out to be essential due to the architectural complexity of neurons exemplified by a relatively small somal size and an extensive network of projections and connections, Thus far, RBPs have been shown to be indispensable for several aspects of neurogenesis, neurite outgrowth, synapse formation, and plasticity. Consequently, perturbation of their function is central in the etiology of an ever-growing spectrum of neurological diseases, including fragile X syndrome and the neurodegenerative disorders frontotemporal lobar degeneration and amyotrophic lateral sclerosis.展开更多
Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievi...Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.展开更多
基金funded by grants from the Greek General Secretariat for Research and Development,Ministry of Education
文摘In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively known as the ribonome, are tightly controlled and carried out by a plethora of trans-acting RNA-binding proteins （RBPs） that bind to specific cis elements throughout the RNA sequence. Within the nervous system, the role of RBPs in brain function turns out to be essential due to the architectural complexity of neurons exemplified by a relatively small somal size and an extensive network of projections and connections, Thus far, RBPs have been shown to be indispensable for several aspects of neurogenesis, neurite outgrowth, synapse formation, and plasticity. Consequently, perturbation of their function is central in the etiology of an ever-growing spectrum of neurological diseases, including fragile X syndrome and the neurodegenerative disorders frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
基金This work was supported by the National Natural Science Foundation of China(No.81860357)the Young Talents Support Program of Yunnan Province,China(Ten Thousand People Plan,YNWR-QNBJ-2019-178).
文摘Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.
