生物
逆转录酶
抄写(语言学)
病毒学
遗传学
机制(生物学)
乙型肝炎病毒
病毒
基因
核糖核酸
语言学
认识论
哲学
作者
Yingpu Yu,Maximilian A. Kass,Mengyin Zhang,Noor Youssef,Catherine A. Freije,Kelly P. Brock,Lauren C. Aguado,Leon Louis Seifert,Sanjana Venkittu,Xupeng Hong,Amir Shlomai,Ype P. de Jong,Debora S. Marks,Charles M. Rice,William M. Schneider
出处
期刊:Cell
[Elsevier]
日期:2024-05-01
标识
DOI:10.1016/j.cell.2024.04.008
摘要
Hepatitis B virus (HBV) is a small double-stranded DNA virus that chronically infects 296 million people. Over half of its compact genome encodes proteins in two overlapping reading frames, and during evolution, multiple selective pressures can act on shared nucleotides. This study combines an RNA-based HBV cell culture system with deep mutational scanning (DMS) to uncouple cis- and trans-acting sequence requirements in the HBV genome. The results support a leaky ribosome scanning model for polymerase translation, provide a fitness map of the HBV polymerase at single-nucleotide resolution, and identify conserved prolines adjacent to the HBV polymerase termination codon that stall ribosomes. Further experiments indicated that stalled ribosomes tether the nascent polymerase to its template RNA, ensuring cis-preferential RNA packaging and reverse transcription of the HBV genome.
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