Sequence determinants of the folding properties of box C/D kink-turns in RNA

TY - JOUR

T1 - Sequence determinants of the folding properties of box C/D kink-turns in RNA

AU - Ashraf, Saira

AU - Huang, Lin

AU - Lilley, David M. J.

N1 - Funding: Cancer Research UK for financial support (program grant A18604).

PY - 2017/12

Y1 - 2017/12

N2 - Folding properties differ markedly between kink-turns (k-turns) that have different biological function. While ribosomal and riboswitch k-turns generally fold into their kinked conformation on addition of metal ions, box C/D snoRNP k-turns remain completely unfolded under these conditions, although they fold on addition of L7Ae protein. Sequence elements have been systematically exchanged between a standard ribosomal k-turn (Kt-7) that folds on addition of metal ions, and a box C/D k-turn. Folding was studied using fluorescence resonance energy transfer and gel electrophoresis. Three sequence elements each contribute in an approximately additive manner to the different folding properties of Kt-7 and box C/D k-turns from archaea. Bioinformatic analysis indicates that k-turn sequences evolve sequences that suit their folding properties to their biological function. The majority of ribosomal and riboswitch k-turns have sequences allowing unassisted folding in response to the presence of metal ions. By contrast, box C/D k-turns have sequences that require the binding of proteins to drive folding into the kinked conformation, consistent with their role in the assembly of the box C/D snoRNP apparatus. The rules governing the influence of sequence on folding properties can be applied to other standard k-turns to predict their folding characteristics.

AB - Folding properties differ markedly between kink-turns (k-turns) that have different biological function. While ribosomal and riboswitch k-turns generally fold into their kinked conformation on addition of metal ions, box C/D snoRNP k-turns remain completely unfolded under these conditions, although they fold on addition of L7Ae protein. Sequence elements have been systematically exchanged between a standard ribosomal k-turn (Kt-7) that folds on addition of metal ions, and a box C/D k-turn. Folding was studied using fluorescence resonance energy transfer and gel electrophoresis. Three sequence elements each contribute in an approximately additive manner to the different folding properties of Kt-7 and box C/D k-turns from archaea. Bioinformatic analysis indicates that k-turn sequences evolve sequences that suit their folding properties to their biological function. The majority of ribosomal and riboswitch k-turns have sequences allowing unassisted folding in response to the presence of metal ions. By contrast, box C/D k-turns have sequences that require the binding of proteins to drive folding into the kinked conformation, consistent with their role in the assembly of the box C/D snoRNP apparatus. The rules governing the influence of sequence on folding properties can be applied to other standard k-turns to predict their folding characteristics.

KW - RNA structure

KW - snoRNP

KW - k-turns

KW - metal ions

KW - L7Ae

U2 - 10.1261/rna.063453.117

DO - 10.1261/rna.063453.117

M3 - Article

C2 - 28956757

SN - 1355-8382

VL - 23

SP - 1927

EP - 1935

JO - RNA: a Publication of the RNA Society

JF - RNA: a Publication of the RNA Society

IS - 12

ER -