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Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...

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Related Experiment Video

Updated: Jun 12, 2026

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
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A nanopore-based HIV-1 reference epitranscriptome.

Michael S Bosmeny1, Adrian A Pater1, Li Zhang2

  • 1Department of Biochemistry, Wake Forest University, School of Medicine, Winston-Salem, NC 27101, United States.

Nucleic Acids Research
|March 19, 2026
PubMed
Summary
This summary is machine-generated.

Researchers mapped RNA modifications in HIV-1, creating a reference epitranscriptome. This benchmark advances HIV-1 epitranscriptomics and provides a roadmap for studying other pathogens.

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Area of Science:

  • Molecular Biology
  • Virology
  • Genomics

Background:

  • Post-transcriptional modifications, forming the epitranscriptome, are crucial for RNA metabolism and gene regulation.
  • Challenges in mapping and functional characterization hinder epitranscriptomic studies.
  • Establishing reference epitranscriptomes is vital for data benchmarking and advancing the field.

Purpose of the Study:

  • To establish a reference epitranscriptome for human immunodeficiency virus 1 (HIV-1).
  • To map multiple RNA modifications at nucleotide resolution using advanced sequencing technology.
  • To provide a benchmark for HIV-1 epitranscriptomic research and a model for other pathogens.

Main Methods:

  • Sequencing of a model HIV-1 genome from infected T cells using nanopore technology.
  • Multiplexed base calling to map N6-methyladenosine (m6A), 5-methylcytidine, pseudouridine, inosine, and 2'-O-methyl modifications.
  • Correction of modification miscalling using synthetic RNA fragments and validation with an inhibitor.

Main Results:

  • A sense and preliminary antisense HIV-1 epitranscriptome were generated.
  • Modification patterns were consistent across different conditions, including combination antiretroviral therapy and in HIV-1 virions.
  • Substantial conservation of m6A modifications was observed in circulating HIV-1 strains from infected individuals.
  • Spliced transcript-dependent modification levels were identified.

Conclusions:

  • The study provides the first reference epitranscriptome for HIV-1, establishing a crucial benchmark.
  • The developed approach offers a roadmap for creating reference epitranscriptomes for other viruses and pathogens.
  • Findings advance the understanding of HIV-1 RNA modifications and their conservation in clinical strains.