Viruses, Vol. 12, Pages 1108: A New Approach to 3D Modeling of Inhomogeneous Populations of Viral Regulatory RNA

Viruses, Vol. 12, Pages 1108: A New Approach to 3D Modeling of Inhomogeneous Populations of Viral Regulatory RNA Viruses doi: 10.3390/v12101108 Authors: Osmer Singh Boris-Lawrie 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 ...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research