title: Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.
abstract: Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites.
authors.affiliation: Department of Chemistry and Biochemistry.
authors.forename: Andy
authors.initials: A
authors.lastname: Phan
authors.affiliation: Department of Chemistry and Biochemistry.
authors.forename: Katherine
authors.initials: K
authors.lastname: Mailey
authors.affiliation: Department of Chemistry and Biochemistry.
authors.forename: Jessica
authors.initials: J
authors.lastname: Saeki
authors.affiliation: Department of Chemistry and Biochemistry.|Department of Microbiology and Plant Biology, University of Oklahoma, Norman, Oklahoma 73019, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Chemistry and Biochemistry susan.schroeder@ou.edu.|Department of Microbiology and Plant Biology, University of Oklahoma, Norman, Oklahoma 73019, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Schroeder
mesh_terms: D020029:Base Pairing; D003596:Cytosine / Q000737:chemistry; D030561:Databases, Nucleic Acid; D009690:Nucleic Acid Conformation; D011743:Pyrimidines / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry*; D013816:Thermodynamics; D014498:Uracil / Q000737:chemistry
chemical_list: D011743:Pyrimidines; D012367:RNA, Viral; D014498:Uracil; D003596:Cytosine
keywords: RNA secondary structure prediction; internal ribosome entry site; pyrimidine-rich internal loops; thermodynamics; viral RNA