RRC ID 50414
著者 Szostak E, García-Beyaert M, Guitart T, Graindorge A, Coll O, Gebauer F.
タイトル Hrp48 and eIF3d contribute to msl-2 mRNA translational repression.
ジャーナル Nucleic Acids Res
Abstract Translational repression of msl-2 mRNA in females of Drosophila melanogaster is an essential step in the regulation of X-chromosome dosage compensation. Repression is orchestrated by Sex-lethal (SXL), which binds to both untranslated regions (UTRs) of msl-2 and inhibits translation initiation by poorly understood mechanisms. Here we identify Hrp48 as a SXL co-factor. Hrp48 binds to the 3' UTR of msl-2 and is required for optimal repression by SXL. Hrp48 interacts with eIF3d, a subunit of the eIF3 translation initiation complex. Reporter and RNA chromatography assays showed that eIF3d binds to msl-2 5' UTR, and is required for efficient translation and translational repression of msl-2 mRNA. In line with these results, eIF3d depletion -but not depletion of other eIF3 subunits- de-represses msl-2 expression in female flies. These data are consistent with a model where Hrp48 inhibits msl-2 translation by targeting eIF3d. Our results uncover an important step in the mechanism of msl-2 translation regulation, and illustrate how general translation initiation factors can be co-opted by RNA binding proteins to achieve mRNA-specific control.
巻・号 46(8)
ページ 4099-4113
公開日 2018-5-4
DOI 10.1093/nar/gky246
PII 4959919
PMID 29635389
PMC PMC5934621
MeSH 5' Untranslated Regions Animals DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Drosophila Proteins / physiology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Eukaryotic Initiation Factor-3 / antagonists & inhibitors Eukaryotic Initiation Factor-3 / metabolism* Female Gene Expression Regulation* Heterogeneous-Nuclear Ribonucleoproteins / metabolism* Heterogeneous-Nuclear Ribonucleoproteins / physiology Nuclear Proteins / genetics* Nuclear Proteins / metabolism Protein Biosynthesis* Ribonucleoproteins / metabolism Transcription Factors / genetics* Transcription Factors / metabolism
IF 11.502
引用数 5
リソース情報
ショウジョウバエ 10161R-3