目的探索铁自噬相关蛋白ELAV样RNA结合蛋白1(ELAV like RNA binding protein 1,ELAVL1)在多发性骨髓瘤(multiple myeloma,MM)中的表达,明确其在MM诊断及预后中的价值。方法首先利用GEO、TCGA数据库资料分析ELAVL1在健康对照及MM患者中...目的探索铁自噬相关蛋白ELAV样RNA结合蛋白1(ELAV like RNA binding protein 1,ELAVL1)在多发性骨髓瘤(multiple myeloma,MM)中的表达,明确其在MM诊断及预后中的价值。方法首先利用GEO、TCGA数据库资料分析ELAVL1在健康对照及MM患者中的表达,进一步用qRT-PCR在临床样本中进行验证。受试者工作特征(receiver operating characteristic,ROC)曲线及Kaplan-Meier法评估ELAVL1在MM患者诊断及预后中的价值;单因素及多因素COX分析探索影响MM预后的独立危险因素。最后,利用DAVID在线网站对差异基因进行功能富集分析。结果ELAVL1在初发MM及难治复发MM中表达增高(P<0.001),MM患者的ISS分期越高,ELAVL1的表达水平越高(P<0.01)。与20例健康对照相比,ELAVL1表达水平在28例初发MM患者标本中增高(P<0.001)。ROC曲线分析发现,ELAVL1的表达水平可以有效区分初发MM和健康对照(P<0.001)及单克隆免疫球蛋白增多症(monoclonal gammopathy of undetermined significance,MGUS)患者(P=0.0002)。生存分析发现,ELAVL1高表达组患者无进展生存时间(progression-free survival,PFS)(P=0.0141)及总体生存时间(overall survival time,OS)(P=0.0080)均短于ELAVL1低表达组患者。单因素分析及多因素分析发现,ELVAL1高表达是MM患者预后不良的独立危险因素(P=0.0050)。功能富集分析提示,差异基因主要富集于Hippo信号通路及MAPK信号通路。结论ELAVL1在MM中表达增高,其表达水平可以作为MM诊断及预后不良的标志物。ELAVL1可能通过Hippo信号通路及MAPK信号通路影响MM的发生发展。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
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
Bombyx mori ELAV-like-1(BmEL-1)and B.mori ELAV-like-2(BmEL-2)are 2 members of the ELAV-like family of RNA-binding proteins.Mutations in Bmel-1 and Bmel-2 resulted in 5.8%and 28.5%decreases in larval weight on the 3rd ...Bombyx mori ELAV-like-1(BmEL-1)and B.mori ELAV-like-2(BmEL-2)are 2 members of the ELAV-like family of RNA-binding proteins.Mutations in Bmel-1 and Bmel-2 resulted in 5.8%and 28.5%decreases in larval weight on the 3rd day of the 5th instar larva(L5D3),respectively.Triglycerides(TG)are the most important energy resource and are the main component of neutral fat(NF)in animals.To investigate the role of Bmelav-like genes in the synthesis and decomposition of TG,transcriptomic,and metabolic analyses were performed on the whole bodies on the 1st day of the 2nd instar larvae(L2D1)and on fat bodies on L5D3 of Bmel-1^(−)and Bmel-2^(−)mutants,respectively.As compared with the control silkworm,differentially expressed genes generated in both mutants were mainly enriched in lysine degradation,fatty acid(FA)metabolism,and unsaturated FAs biosynthesis.The diglyceride and phosphatide contents were significantly lower in Bmel-1^(−)and Bmel-2^(−)fat bodies than those of the control group.Consistently,the NF content of both mutants’fat bodies were reduced by 50%and 60%,respectively.BmEL-2 positively regulates BmAGPATγ(B.mori 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma,LOC101741736)and BmFaF2(B.mori fatty acid synthetase-associated factor 2,LOC101739090)expression by binding to the specific regions of their 3′untranslated regions in BmN cells.This study suggests that BmEL-2 may be an important regulator of BmAGPAT γand BmFAF2 expression and thereby participates in TG metabolism in the silkworm fat body.展开更多
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.
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supported by the Natural Science Foundation of Jiangsu province(grant No.BK20221294)National Natural Science Foundation of China(grant No.32072790 and 31702056)Jiangsu Graduate Student Innovation Funding Project(SJCX22_1986,SJCX24_2567,SJCX22_1982).
文摘Bombyx mori ELAV-like-1(BmEL-1)and B.mori ELAV-like-2(BmEL-2)are 2 members of the ELAV-like family of RNA-binding proteins.Mutations in Bmel-1 and Bmel-2 resulted in 5.8%and 28.5%decreases in larval weight on the 3rd day of the 5th instar larva(L5D3),respectively.Triglycerides(TG)are the most important energy resource and are the main component of neutral fat(NF)in animals.To investigate the role of Bmelav-like genes in the synthesis and decomposition of TG,transcriptomic,and metabolic analyses were performed on the whole bodies on the 1st day of the 2nd instar larvae(L2D1)and on fat bodies on L5D3 of Bmel-1^(−)and Bmel-2^(−)mutants,respectively.As compared with the control silkworm,differentially expressed genes generated in both mutants were mainly enriched in lysine degradation,fatty acid(FA)metabolism,and unsaturated FAs biosynthesis.The diglyceride and phosphatide contents were significantly lower in Bmel-1^(−)and Bmel-2^(−)fat bodies than those of the control group.Consistently,the NF content of both mutants’fat bodies were reduced by 50%and 60%,respectively.BmEL-2 positively regulates BmAGPATγ(B.mori 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma,LOC101741736)and BmFaF2(B.mori fatty acid synthetase-associated factor 2,LOC101739090)expression by binding to the specific regions of their 3′untranslated regions in BmN cells.This study suggests that BmEL-2 may be an important regulator of BmAGPAT γand BmFAF2 expression and thereby participates in TG metabolism in the silkworm fat body.
