The Drosophila hnRNP F/H homolog Glorund recruits dFMRP to inhibit nanos translation elongation.

TitleThe Drosophila hnRNP F/H homolog Glorund recruits dFMRP to inhibit nanos translation elongation.
Publication TypeJournal Article
Year of Publication2022
AuthorsPeng, Y, Gavis, ER
JournalNucleic Acids Res
Volume50
Issue12
Pagination7067-7083
Date Published2022 Jul 08
ISSN1362-4962
KeywordsAnimals, Drosophila, Drosophila Proteins, Fragile X Mental Retardation Protein, Heterogeneous-Nuclear Ribonucleoprotein Group F-H, Protein Biosynthesis, RNA-Binding Proteins
Abstract

<p>Translational control of maternal mRNAs generates spatial and temporal patterns of protein expression necessary to begin animal development. Translational repression of unlocalized nanos (nos) mRNA in late-stage Drosophila oocytes by the hnRNP F/H homolog, Glorund (Glo), is important for embryonic body patterning. While previous work has suggested that repression occurs at both the translation initiation and elongation phases, the molecular mechanism by which Glo regulates nos translation remains elusive. Here, we have identified the Drosophila fragile X mental retardation protein, dFMRP, as a Glo interaction partner with links to the translational machinery. Using an oocyte-based in vitro translation system, we confirmed that Glo regulates both initiation and elongation of a nos translational reporter and showed that dFMRP specifically represses translation elongation and promotes ribosome stalling. Furthermore, we combined mutational analysis and in vivo and in vitro binding assays to show that Glo's qRRM2 domain specifically and directly interacts with dFMRP. Our findings suggest that Glo regulates nos translation elongation by recruiting dFMRP and that Glo's RNA-binding domains can also function as protein-protein interaction interfaces critical for its regulatory functions. Additionally, they reveal a mechanism for targeting dFMRP to specific transcripts.</p>

DOI10.1093/nar/gkac500
Alternate JournalNucleic Acids Res
PubMed ID35699205
PubMed Central IDPMC9262583
Grant ListR35 GM126967 / GM / NIGMS NIH HHS / United States