Dold, A., Han, H., Liu, N., Hildebrandt, A., Brüggemann, M., Rücklé, C., Hänel, H., Busch, A., Beli, P., Zarnack, K., König, J., Roignant, J.Y., Lasko, P. (2020). Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation.  PLoS Genet. 16(1): e1008581.

FBrf0244799

Research paper

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.

PMC7001992 (PMC) (EuropePMC)