The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells.

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yaxu Liang, Xuejiao Zhu, Ruhao Zhuo, Ning Peng, Shuyu Chen, Shimeng Huang, Zhending Gan, Jun Qi, Zhibo Wang, Bin Li, Xiang Zhong
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引用次数: 0

Abstract

N6-methyladenosine (m6A), the most abundant mRNA modification, regulates various mRNA metabolism to affect numerous physiological processes, including immune response. Interestingly, many RNA viruses contain internal m6A modifications that contribute to viral replication and innate immune escape process, but its mechanisms remain unclear. Porcine rotavirus (PoRV) is a common cause of diarrhea and gastroenteritis in piglets. Here, we first revealed the m6A methylation profile on the PoRV genome. PoRV infection significantly reduced methyltransferase METTL3 expression and induced nuclear-cytoplasmic translocation of METTL3. The structural protein VP6 of PoRV can co-localize with METTL3 in the cytoplasm and bind to METTL3 protein, suggesting that PoRV hijacked the host METTL3 to achieve m6A methylation. On the contrary, knockdown of Mettl3 or Ythdf2 in IPEC cells inhibited the replication of PoRV. Mechanistically, silencing of Mettl3 or Ythdf2 enhanced the expression of IRF2 and IFI44L via an increase of mRNA stability of Irf2 and Ifi44l. Furthermore, knockdown of Irf2 and Ifi44l promoted viral replication in IPEC cells. In conclusion, PoRV took full advantage of METTL3 to promote replication, in turn, host reduced own m6A methylation to enhance IRF2 and IFI44L to restrain virus infection, suggesting a love-hate relationship between virus and host, and providing novel targets for developing antiviral drugs in the pig industry.

m6A RNA甲基化在猪轮状病毒与宿主细胞的爱恨关系中的作用。
n6 -甲基腺苷(m6A)是最丰富的mRNA修饰,调节各种mRNA代谢,影响包括免疫应答在内的许多生理过程。有趣的是,许多RNA病毒含有内部m6A修饰,这些修饰有助于病毒复制和先天免疫逃逸过程,但其机制尚不清楚。猪轮状病毒(PoRV)是仔猪腹泻和胃肠炎的常见病因。在这里,我们首次揭示了PoRV基因组上的m6A甲基化谱。PoRV感染显著降低甲基转移酶METTL3的表达,诱导METTL3核细胞质易位。PoRV的结构蛋白VP6可以在细胞质中与METTL3共定位并结合到METTL3蛋白上,表明PoRV劫持了宿主METTL3实现了m6A的甲基化。相反,在IPEC细胞中敲低Mettl3或Ythdf2可抑制PoRV的复制。从机制上讲,沉默Mettl3或Ythdf2通过增加IRF2和IFI44L mRNA的稳定性来增强IRF2和IFI44L的表达。此外,Irf2和ifi441的敲低促进了IPEC细胞中的病毒复制。综上所述,PoRV充分利用METTL3促进复制,反过来,宿主降低自身m6A甲基化,增强IRF2和IFI44L,从而抑制病毒感染,表明病毒与宿主之间存在爱恨交织的关系,为养猪业开发抗病毒药物提供了新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell and Bioscience
Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
10.70
自引率
0.00%
发文量
187
审稿时长
>12 weeks
期刊介绍: Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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