Next Article in Journal
Overview of the Nucleic-Acid Binding Properties of the HIV-1 Nucleocapsid Protein in Its Different Maturation States
Next Article in Special Issue
Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates
Previous Article in Journal
A Functional K+ Channel from Tetraselmis Virus 1, a Member of the Mimiviridae
Previous Article in Special Issue
Abrogating ALIX Interactions Results in Stuttering of the ESCRT Machinery
Open AccessArticle

A New Approach to 3D Modeling of Inhomogeneous Populations of Viral Regulatory RNA

1
Department of Astronomy, The Ohio State University, Columbus, OH 43210, USA
2
Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USA
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(10), 1108; https://doi.org/10.3390/v12101108
Received: 3 July 2020 / Revised: 24 September 2020 / Accepted: 27 September 2020 / Published: 29 September 2020
(This article belongs to the Special Issue The 11th International Retroviral Nucleocapsid and Assembly Symposium)
Tertiary structure (3D) is the physical context of RNA regulatory activity. Retroviruses are RNA viruses that replicate through the proviral DNA intermediate transcribed by hosts. Proviral transcripts form inhomogeneous populations due to variable structural ensembles of overlapping regulatory RNA motifs in the 5′-untranslated region (UTR), which drive RNAs to be spliced or translated, and/or dimerized and packaged into virions. Genetic studies and structural techniques have provided fundamental input constraints to begin predicting HIV 3D conformations in silico. Using SimRNA and sets of experimentally-determined input constraints of HIVNL4-3 trans-activation responsive sequence (TAR) and pairings of unique-5′ (U5) with dimerization (DIS) or AUG motifs, we calculated a series of 3D models that differ in proximity of 5′-Cap and the junction of TAR and PolyA helices; configuration of primer binding site (PBS)-segment; and two host cofactors binding sites. Input constraints on U5-AUG pairings were most compatible with intramolecular folding of 5′-UTR motifs in energetic minima. Introducing theoretical constraints predicted metastable PolyA region drives orientation of 5′-Cap with TAR, U5 and PBS-segment helices. SimRNA and the workflow developed herein provides viable options to predict 3D conformations of inhomogeneous populations of large RNAs that have been intractable to conventional ensemble methods. View Full-Text
Keywords: 5′-cap; centroid; complex 5′-untranslated region; intramolecular folding; medoid; retrovirus; RNA structure ensemble; supercomputer cluster 5′-cap; centroid; complex 5′-untranslated region; intramolecular folding; medoid; retrovirus; RNA structure ensemble; supercomputer cluster
Show Figures

Graphical abstract

MDPI and ACS Style

Osmer, P.S.; Singh, G.; Boris-Lawrie, K. A New Approach to 3D Modeling of Inhomogeneous Populations of Viral Regulatory RNA. Viruses 2020, 12, 1108.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop