Epstein-Barr 病毒非编码 RNA EBER1 促进核糖体蛋白旁系同源物的表达,从而促进氧化磷酸化。
Epstein-Barr virus noncoding RNA EBER1 promotes the expression of a ribosomal protein paralog to boost oxidative phosphorylation.
发表日期:2024 Aug
作者:
Sita Paudel, Nara Lee
来源:
JOURNAL OF MEDICAL VIROLOGY
摘要:
EB 病毒 (EBV) 是一种非常成功的病原体,可感染约 95% 的成年人,并与多种癌症和自身免疫性疾病有关。潜伏感染细胞中最丰富的病毒因子不是蛋白质,而是一种称为 EBV 编码 RNA 1 (EBER1) 的非编码 RNA。尽管 EBER1 的含量非常丰富并且在四十多年前就被发现,但 EBER1 的功能仍然难以捉摸。 EBER1 与核糖体蛋白 L22 相互作用,后者通常会抑制其旁系同源物 L22 样 1 (L22L1) 的表达。在这里,我们表明,当L22结合EBER1时,它不能抑制L22L1,导致L22L1被表达并掺入核糖体中。我们进一步表明,含有 L22L1 的核糖体优先翻译参与氧化磷酸化途径的 mRNA。此外,L22L1 的上调对于 EBV 感染后静息 B 细胞的生长转化和永生化是必不可少的。总而言之,我们的结果表明 EBER1 的功能是在翻译水平上调节宿主基因表达,从而绕过了宿主基因转录失调的需要。© 2024 作者。 《医学病毒学杂志》由 Wiley periodicals LLC 出版。
Epstein-Barr virus (EBV) is a highly successful pathogen that infects ~95% of the adult population and is associated with diverse cancers and autoimmune diseases. The most abundant viral factor in latently infected cells is not a protein but a noncoding RNA called EBV-encoded RNA 1 (EBER1). Even though EBER1 is highly abundant and was discovered over forty years ago, the function of EBER1 has remained elusive. EBER1 interacts with the ribosomal protein L22, which normally suppresses the expression of its paralog L22-like 1 (L22L1). Here we show that when L22 binds EBER1, it cannot suppress L22L1, resulting in L22L1 being expressed and incorporated into ribosomes. We further show that L22L1-containing ribosomes preferentially translate mRNAs involved in the oxidative phosphorylation pathway. Moreover, upregulation of L22L1 is indispensable for growth transformation and immortalization of resting B cells upon EBV infection. Taken together, our results suggest that the function of EBER1 is to modulate host gene expression at the translational level, thus bypassing the need for dysregulating host gene transcription.© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.