The Unusual Compactness of Viral RNA

Abstract

We present complementary experimental and computational studies of the relative sizes of equal-length long single-stranded (ss) RNA molecules. Comparison of viral, non-viral, coding and non-coding RNAs of length 2117 nucleotides (nt) shows viral RNA to have among the highest gel-mobilities and smallest hydrodynamic radii in solution. Using graph theoretical tools, we demonstrate that the measured sizes are correlated with the compactness of branching patterns in predicted secondary structure ensembles. Compactness is determined by the number and relative positions of 3-helix junctions, and is highly sensitive to the presence of rare higher-order (4 or more helix) junctions. RNAs from spherical viruses possess greater numbers of higher-order junctions than random sequences or those from non-spherical viruses. The importance of secondary structure topography as a determinant of global RNA size, and implications of compactness for viral assembly will be discussed.The accompanying native gel-electrophoresis image comparing RNAs of identical length shows they have significantly different hydrodynamic properties. Lane 1 contains the viral RNA, mutated viral sequences are in lanes 2-4, and lanes 5-9 show equal-length transcripts from arbitrary sections of the yeast genome. Lane 6 shows that RNAs with different sequences although mixed before electrophoresis are separable.View Large Image | View Hi-Res Image | Download PowerPoint Slide