Cup is essential foroskarmRNA translational repression during earlyDrosophilaoogenesis

ABSTRACT The proper timing of mRNA translation is crucial across many biological systems for processes such as intercellular communication, body pattern formation, and morphogenesis. The main D. melanogaster posterior determinant, oskar , is maternally transcribed, but only translated when properly localized at the oocyte’s posterior cortex. Bruno 1 and Cup are two effector proteins known to participate in multiple aspects of oskar mRNA regulation. Current model describes a mechanism in which Bruno 1 is necessary for Cup’s recruitment to oskar mRNA, and Bruno 1 is indispensable for its translational repression. Here, we reveal that the Bruno 1-Cup interaction, as well as their interdependent influence on each other’s mRNA and protein expression, lead to precise oskar mRNA regulation during early oogenesis. We show that these factors stably associate with the oskar mRNA in vivo , but surprisingly, Bruno 1’s stable association with oskar mRNA depends on Cup, while Bruno 1 is not necessary for Cup association to oskar mRNA. During early oogenesis, Cup, not Bruno 1, is the essential factor for oskar mRNA repression. Cup is a crucial P-body member that maintains proper P-body morphology during oogenesis, as well as it is necessary for oskar mRNA’s association with P-bodies, thus driving the translational repression and stability of oskar mRNA. Our experimental results collectively suggest a regulatory mechanism where a feedback loop between Bruno 1 and Cup coordinates oskar mRNA regulation in the egg chamber allowing for proper development to occur.