Oskar allowsnanosmRNA translation inDrosophilaembryos by preventing its deadenylation by Smaug/CCR4

Abstract

Anteroposterior patterning of the Drosophila embryo depends on a gradient of Nanos protein arising from the posterior pole. This gradient results from both nanos mRNA translational repression in the bulk of the embryo and translational activation of nanos mRNA localized at the posterior pole. Two mechanisms of nanos translational repression have been described, at the initiation step and after this step. Here we identify a novel level of nanos translational control. We show that the Smaug protein bound to the nanos 3Ј UTR recruits the deadenylation complex CCR4-NOT, leading to rapid deadenylation and subsequent decay of nanos mRNA. Inhibition of deadenylation causes stabilization of nanos mRNA, ectopic synthesis of Nanos protein and head defects. Therefore, deadenylation is essential for both translational repression and decay of nanos mRNA. We further propose a mechanism for translational activation at the posterior pole. Translation of nanos mRNA at the posterior pole depends on oskar function. We show that Oskar prevents the rapid deadenylation of nanos mRNA by precluding its binding to Smaug, thus leading to its stabilization and translation. This study provides insights into molecular mechanisms of regulated deadenylation by specific proteins and demonstrates its importance in development.

Arabidopsis Deadenylases AtCAF1a and AtCAF1b Play Overlapping and Distinct Roles in Mediating Environmental Stress Responses

“…In Drosophila, the interaction of CAF1 with the RNA-binding protein Smaug allows for the specific targeting of the CCR4-CAF1 complex to Hsp83 and nanos mRNAs (Semotok et al, 2005;Zaessinger et al, 2006). Additionally, in yeast the Figure 7.…”

Contrôle du développement embryonnaire par des petits ARN issus de transposons

“…À l'inverse, l'ARNm nanos présent dans le reste de l'embryon doit être absolument réprimé pour le développement correct de la tête et du thorax [6]. Au niveau moléculaire, nous avons montré que cette répression dans le corps de l'embryon est en partie dépendante de la déadénylase CCR4 recrutée par Smaug, une protéine de liaison à l'ARN, sur l'ARNm nanos [7].…”

Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3′ UTR

“…In some cases, repressors act instead by sequestering target mRNAs into large silencing messenger ribonucleoproteins (mRNPs) (Nakamura et al 2001;Chekulaeva et al 2006). Still others negatively regulate their target mRNAs by recruiting the CCR4 deadenylase complex (Semotok et al 2005;Zaessinger et al 2006;Chicoine et al 2007;Kadryova et al 2007). Targeting also requires mechanisms to alleviate repression and activate translation in the appropriate spatial domain.…”

“…Relatively less is known about these positive regulatory processes. Osk contributes to derepressing nos by preventing its association with Smaug, and thus with CCR4 deadenylase (Zaessinger et al 2006). Activation of grk mRNA translation at the antero-dorsal cortex of the developing oocyte is mediated by poly(A)-binding protein 55D (PABP55D) in association with Encore (Clouse et al 2008).…”