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

Autoři: Annabelle Dold aff001;  Hong Han aff002;  Niankun Liu aff002;  Andrea Hildebrandt aff003;  Mirko Brüggemann aff005;  Cornelia Rücklé aff005;  Heike Hänel aff004;  Anke Busch aff006;  Petra Beli aff003;  Kathi Zarnack aff005;  Julian König aff004;  Jean-Yves Roignant aff001;  Paul Lasko aff002
Působiště autorů: RNA Epigenetics, Institute of Molecular Biology, Mainz, Germany aff001;  Department of Biology, McGill University, Montréal, Québec, Canada aff002;  Chromatin Biology and Epigenetics, Institute of Molecular Biology, Mainz, Germany aff003;  Genomic Views of Splicing Regulation, Institute of Molecular Biology, Mainz, Germany aff004;  Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany aff005;  Bioinformatics Core Facility, Institute of Molecular Biology, Mainz, Germany aff006;  Center for Integrative Genomics, Génopode Building, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland aff007;  Department of Human Genetics, Radboud University Medical Center, GA Nijmegen, Netherlands aff008
Vyšlo v časopise: Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation. PLoS Genet 16(1): e32767. doi:10.1371/journal.pgen.1008581
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008581


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.

Klíčová slova:

3' UTR – Drosophila melanogaster – Embryos – Messenger RNA – Oocytes – Ovaries – Protein translation – Sequence motif analysis


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