Direct role for the Drosophila GIGYF protein in 4EHP-mediated mRNA repression
| Autor: | Elisa Izaurralde, Sigrun Helms, Vincenzo Ruscica, Daniel Peter, Praveen Bawankar, Cátia Igreja |
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| Rok vydání: | 2019 |
| Předmět: |
RNA Caps
RNA Stability Down-Regulation Repressor Biology Conserved sequence DEAD-box RNA Helicases 03 medical and health sciences Ribonucleases 0302 clinical medicine Genes Reporter Endopeptidases RNA and RNA-protein complexes Genetics Protein biosynthesis Animals Drosophila Proteins Amino Acid Sequence RNA Messenger Psychological repression Conserved Sequence 030304 developmental biology 0303 health sciences Messenger RNA Sequence Homology Amino Acid Effector EIF4E RNA-Binding Proteins RNA Helicase A Cell biology Repressor Proteins Drosophila melanogaster Eukaryotic Initiation Factor-4E Gene Expression Regulation RNA Cap-Binding Proteins Multiprotein Complexes Protein Biosynthesis Sequence Alignment 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkz429 |
| Popis: | The eIF4E-homologous protein (4EHP) is a translational repressor that competes with eIF4E for binding to the 5′-cap structure of specific mRNAs, to which it is recruited by protein factors such as the GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins (GIGYF). Several experimental evidences suggest that GIGYF proteins are not merely facilitating 4EHP recruitment to transcripts but are actually required for the repressor activity of the complex. However, the underlying molecular mechanism is unknown. Here, we investigated the role of the uncharacterized Drosophila melanogaster (Dm) GIGYF protein in post-transcriptional mRNA regulation. We show that, when in complex with 4EHP, Dm GIGYF not only elicits translational repression but also promotes target mRNA decay via the recruitment of additional effector proteins. We identified the RNA helicase Me31B/DDX6, the decapping activator HPat and the CCR4–NOT deadenylase complex as binding partners of GIGYF proteins. Recruitment of Me31B and HPat via discrete binding motifs conserved among metazoan GIGYF proteins is required for downregulation of mRNA expression by the 4EHP–GIGYF complex. Our findings are consistent with a model in which GIGYF proteins additionally recruit decapping and deadenylation complexes to 4EHP-containing RNPs to induce translational repression and degradation of mRNA targets. |
| Databáze: | OpenAIRE |
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