Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

PLoS Genet. 2020 Jan 24;16(1):e1008581. doi: 10.1371/journal.pgen.1008581. eCollection 2020 Jan.

Abstract

Makorins are evolutionary conserved proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3' UTR in a region adjacent to A-rich sequences. Using Drosophila S2R+ cultured cells we show that this binding site overlaps with a Bruno1 (Bru1) responsive element (BREs) that regulates osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3' UTR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Body Patterning*
  • Cell Line
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ovary / metabolism
  • Protein Binding
  • RNA-Binding Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mkrn1 protein, Drosophila
  • RNA-Binding Proteins
  • bru1 protein, Drosophila
  • osk protein, Drosophila