RRC ID 57091
Author Liao SE, Kandasamy SK, Zhu L, Fukunaga R.
Title DEAD-box RNA helicase Belle posttranscriptionally promotes gene expression in an ATPase activity-dependent manner.
Journal RNA
Abstract Drosophila Belle (human ortholog DDX3) is a conserved DEAD-box RNA helicase implicated in regulating gene expression. However, the molecular mechanisms by which Belle/DDX3 regulates gene expression are poorly understood. Here we performed systematic mutational analysis to determine the contributions of conserved motifs within Belle to its in vivo function. We found that Belle RNA-binding and RNA-unwinding activities and intrinsically disordered regions (IDRs) are required for Belle in vivo function. Expression of Belle ATPase mutants that cannot bind, hydrolyze, or release ATP resulted in dominant toxic phenotypes. Mechanistically, we discovered that Belle up-regulates reporter protein level when tethered to reporter mRNA, without corresponding changes at the mRNA level, indicating that Belle promotes translation of mRNA that it binds. Belle ATPase activity and amino-terminal IDR were required for this translational promotion activity. We also found that ectopic ovary expression of dominant Belle ATPase mutants decreases levels of cyclin proteins, including Cyclin B, without corresponding changes in their mRNA levels. Finally, we found that Belle binds endogenous cyclin B mRNA. We propose that Belle promotes translation of specific target mRNAs, including cyclin B mRNA, in an ATPase activity-dependent manner.
Volume 25(7)
Pages 825-839
Published 2019-7-1
DOI 10.1261/rna.070268.118
PII rna.070268.118
PMID 30979781
PMC PMC6573787
MeSH Adenosine Triphosphatases / genetics Adenosine Triphosphatases / metabolism* Animals Cyclin B / genetics Cyclin B / metabolism DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Eye / growth & development Eye / metabolism Female Infertility, Female Infertility, Male Intrinsically Disordered Proteins / genetics Intrinsically Disordered Proteins / metabolism* Male Phenotype RNA Helicases / genetics RNA Helicases / metabolism* RNA Processing, Post-Transcriptional* RNA, Messenger / genetics RNA, Messenger / metabolism*
IF 3.949
Times Cited 3