한빛사논문
Ohio State University
Alice Baek 1,2,3,12, Ga-Eun Lee 1,2,3,4,12, Sarah Golconda 1,2,3, Asif Rayhan 5, Anastasios A. Manganaris 4,6, Shuliang Chen 1,2, Nagaraja Tirumuru 1,2, Hannah Yu 1,2,3, Shihyoung Kim 1,2,3, Christopher Kimmel 2,4, Olivier Zablocki 7,8, Matthew B. Sullivan 7,8,9, Balasubrahmanyam Addepalli 5, Li Wu 10 & Sanggu Kim 1,2,3,4,11,*
1Center for Retrovirus Research, Ohio State University, Columbus, OH, USA.
2Department of Veterinary Biosciences, Ohio State University, Columbus, OH, USA.
3Infectious Diseases Institute, Ohio State University, Columbus, OH, USA.
4Translational Data Analytics Institute, Ohio State University, Columbus, OH, USA.
5Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, OH, USA.
6Department of Computer Science and Engineering, Ohio State University, Columbus, OH, USA.
7Center of Microbiome Science, Ohio State University, Columbus, OH, USA.
8Department of Microbiology, Ohio State University, Columbus, OH, USA.
9Department of Civil, Environmental and Geodetic Engineering, Ohio State University, Columbus, OH, USA.
10Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
11Center for RNA Biology, Ohio State University, Columbus, OH, USA.
12These authors contributed equally: Alice Baek, Ga-Eun Lee.
*Corresponding author: correspondence to Sanggu Kim
Abstract
Although the significance of chemical modifications on RNA is acknowledged, the evolutionary benefits and specific roles in human immunodeficiency virus (HIV-1) replication remain elusive. Most studies have provided only population-averaged values of modifications for fragmented RNAs at low resolution and have relied on indirect analyses of phenotypic effects by perturbing host effectors. Here we analysed chemical modifications on HIV-1 RNAs at the full-length, single RNA level and nucleotide resolution using direct RNA sequencing methods. Our data reveal an unexpectedly simple HIV-1 modification landscape, highlighting three predominant N6-methyladenosine (m6A) modifications near the 3′ end. More densely installed in spliced viral messenger RNAs than in genomic RNAs, these m6As play a crucial role in maintaining normal levels of HIV-1 RNA splicing and translation. HIV-1 generates diverse RNA subspecies with distinct m6A ensembles, and maintaining multiple of these m6As on its RNAs provides additional stability and resilience to HIV-1 replication, suggesting an unexplored viral RNA-level evolutionary strategy.
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