title: Viral RNAs are unusually compact.
abstract: A majority of viruses are composed of long single-stranded genomic RNA molecules encapsulated by protein shells with diameters of just a few tens of nanometers. We examine the extent to which these viral RNAs have evolved to be physically compact molecules to facilitate encapsulation. Measurements of equal-length viral, non-viral, coding and non-coding RNAs show viral RNAs to have among the smallest sizes in solution, i.e., the highest gel-electrophoretic mobilities and the smallest hydrodynamic radii. Using graph-theoretical analyses we demonstrate that their sizes correlate with the compactness of branching patterns in predicted secondary structure ensembles. The density of branching is determined by the number and relative positions of 3-helix junctions, and is highly sensitive to the presence of rare higher-order junctions with 4 or more helices. Compact branching arises from a preponderance of base pairing between nucleotides close to each other in the primary sequence. The density of branching represents a degree of freedom optimized by viral RNA genomes in response to the evolutionary pressure to be packaged reliably. Several families of viruses are analyzed to delineate the effects of capsid geometry, size and charge stabilization on the selective pressure for RNA compactness. Compact branching has important implications for RNA folding and viral assembly.
authors.affiliation: Department of Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ajaykumar
authors.initials: A
authors.lastname: Gopal
authors.affiliation: Department of Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Defne E
authors.initials: DE
authors.lastname: Egecioglu
authors.affiliation: Department of Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Aron M
authors.initials: AM
authors.lastname: Yoffe
authors.affiliation: Institute of Chemistry & The Fritz Haber Research Center, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
authors.forename: Avinoam
authors.initials: A
authors.lastname: Ben-Shaul
authors.affiliation: Department of Plant Pathology, University of California Riverside, Riverside, California, United States of America.
authors.forename: Ayala L N
authors.initials: AL
authors.lastname: Rao
authors.affiliation: Department of Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Knobler
authors.affiliation: Department of Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Gelbart
mesh_terms: D020029:Base Pairing; D017795:Bromovirus / Q000737:chemistry / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D016679:Genome, Viral; D017909:Levivirus / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D012328:RNA Viruses / Q000737:chemistry / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D013050:Spectrometry, Fluorescence; D014035:Togaviridae / Q000737:chemistry / Q000235:genetics; D019065:Virus Assembly / Q000235:genetics
chemical_list: D012367:RNA, Viral