Back to overview

Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2014
Author Daubner Gerrit, Brummer Annecke, Tocchini Cristina , Gerhardy Stefan , Ciosk Rafal, Zavolan Mihaela, Allain frederic HT,
Project Post-transcriptional regulation of germ cell apoptosis in C. elegans
Show all

Original article (peer-reviewed)

Journal Nucleic Acid Research
Volume (Issue) 42(12)
Page(s) 8092 - 8105
Title of proceedings Nucleic Acid Research
DOI 10.1093/nar/gku445

Open Access

Type of Open Access Publisher (Gold Open Access)


The STAR family comprises ribonucleic acid (RNA)-binding proteins that play key roles in RNA-regulatory processes. RNA recognition is achieved by a KH domain with an additional α-helix (QUA2) that seems to extend the RNA-binding surface to six nucleotides for SF1 (Homo sapiens) and seven nucleotides for GLD-1 (Caenorhabditis elegans). To understand the structural basis of this probable difference in specificity, we determined the solution structure of GLD-1 KH-QUA2 with the complete consensus sequence identified in the tra-2 gene. Compared to SF1, the GLD-1 KH-QUA2 interface adopts a different conformation resulting indeed in an additional sequence-specific binding pocket for a uracil at the 5'end. The functional relevance of this binding pocket is emphasized by our bioinformatics analysis showing that GLD-1 binding sites with this 5'end uracil are more predictive for the functional response of the messenger RNAs to gld-1 knockout. We further reveal the importance of the KH-QUA2 interface in vitro and that its alteration in vivo affects the level of translational repression dependent on the sequence of the GLD-1 binding motif. In conclusion, we demonstrate that the QUA2 domain distinguishes GLD-1 from other members of the STAR family and contributes more generally to the modulation of RNA-binding affinity and specificity of KH domain containing proteins.