Architecture and Secondary Structure of an Entire HIV-1 RNA Genome

By Joseph M. Watts, Kristen K. Dang, R. Gorelick, Christopher W. Leonard, J. Bess, R. Swanstrom, C. Burch, Kevin M. Weeks. Nature, 2009

884 citations recorded by the source corpus.

Single-stranded RNA viruses encompass broad classes of infectious agents and cause the common cold, cancer, AIDS and other serious health threats. Viral replication is regulated at many levels, including the use of conserved genomic RNA structures. Most potential regulatory elements in viral RNA genomes are uncharacterized. Here we report the structure of an entire HIV-1 genome at single nucleotide resolution using SHAPE, a high-throughput RNA analysis technology. The genome encodes protein structure at two levels. In addition to the correspondence between RNA and protein primary sequences, a correlation exists between high levels of RNA structure and sequences that encode inter-domain loops in HIV proteins. This correlation suggests that RNA structure modulates ribosome elongation to promote native protein folding. Some simple genome elements previously shown to be important, including the ribosomal gag-pol frameshift stem-loop, are components of larger RNA motifs. We also identify organizational principles for unstructured RNA regions, including splice site acceptors and hypervariable regions. These results emphasize that the HIV-1 genome and, potentially, many coding RNAs are punctuated by previously unrecognized regulatory motifs and that extensive RNA structure constitutes an important component of the genetic code.

Subfields: Molecular Biology, Plant Science, Virology

View Paper: https://www.semanticscholar.org/paper/3ac17dec5c193af984729bdad5a93605b5fe5d2b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. John S. Mattick
2. Marcel E. Dinger
3. Tim R. Mercer
4. Ryan J. Taft
5. Christopher W. Leonard
6. Ken C. Pang
7. Greggory M. Rice
8. P. Domingo-Calap

In Plant Science

1. Tim R. Mercer
2. John S. Mattick
3. Ryan J. Taft

In Virology

1. P. Domingo-Calap
2. Rafael Sanjuán

Citations in the corpus

• Mechanisms of viral mutation (2016, methodology): “Second, using the RNA structure morel previously determined by selective 20-hydroxyl acylation analyzed by primer extension (SHAPE), we found that this 1 kb region exhibited significantly fewer RNA base-pairs than other regions of the envelope gene [103].”
• Recent advances in RNA structurome (2022, background): “…the advent of sequencing-based enzymatic and chemical probing methods over the last decade, it is now possible to evaluate the structure of an intact viral RNA genome on a genomewide scale, in vitro, and/or in vivo (Burrill et al., 2013; Mauger et al., 2015; Watts et al., 2009; Wu et al., 2013).”
• RNA secondary structure modeling at consistent high accuracy using differential SHAPE (2014, methodology): “This energy penalty was added to the standard 1M7-based pseudo-free energy as implemented in ShapeKnots (Low and Weeks 2010; Hajdin et al. 2013); inclusion of this penalty improved predictions for many RNAs.”
• Non‐coding RNAs: regulators of disease (2010, background): “Indeed, there is increasing evidence to suggest that mRNAs contain extensive RNA structural features [120,121], raising the possibility that, in addition to their protein-coding functions, mRNAs may intrinsically act as regulatory RNAs [122].”