SRE recognition by Smaug family members is mediated by a sterile alpha motif domain, which consists of a cluster of conserved simple resi dues that functions as an RNA binding surface. On binding to target mRNAs Smaug family mem bers repress translation and/or induce transcript decay through their ability to recruit a variety of aspects to a transcript. Such as, Drosophila Smaug can recruit the Cup protein to an mRNA and Cup in turn interacts with all the cap binding protein eIF4E. The Cup eIF4E interaction inhibits translation by blocking eIF4E mediated 40S ribosomal subunit recruitment. Smaug can also recruit Argonaute 1 to an mRNA, thereby repressing translation. Typically, In the past proteins are bound to compact RNAs, this kind of as miRNAs, that perform to target the AGO1 protein to transcripts.
In contrast, Smaug can recruit recommended reading AGO1 in the miRNA independent method. Smaug may also take away an mRNAs poly tail via its ability to recruit the CCR4/NOT deadenylase. Inside the situation of not less than one particular target mRNA this recruitment is imagined to involve a complex containing Smaug as well as the Piwi sort Ago proteins Aubergine and AGO3. This complicated is proposed to bind this target transcript through SREs collectively with web pages com plementary to piwi RNAs that are bound to AGO3 and/or Aubergine. Since the poly tail plays a position in the two initiating translation and stabilizing an mRNA, deadenylase recruitment can, in principle, each block translation and/or induce transcript decay. Smaug has two nicely characterized target mRNAs, nanos and Hsp83.
Smaug represses nanos translation as a result of two SREs inside the nanos 3 untranslated area whereas reduction of Smaug has full report only a modest result on nanos mRNA stability. In contrast, Smaug induces the degradation of Hsp83 mRNA by way of eight SREs while in the Hsp83 open reading frame, when owning no detectable result on Hsp83 translation. Thus, Smaug can dif ferentially regulate the expression of its target mRNAs. nanos and Hsp83 mRNAs are localized to the posterior on the embryo and Smaugs regulation of those two tran scripts is intimately related with their localization. nanos mRNA is inefficiently localized towards the posterior and nanos mRNA that escapes the localization machinery is discovered dis tributed throughout the bulk with the embryo wherever it really is translationally repressed by Smaug. nanos mRNA localized to the posterior just isn’t repressed by Smaug and Nanos protein expression is consequently limited towards the pos terior in the embryo. Hsp83 mRNA is uniformly distributed in early embryos and, as embryogenesis proceeds, Smaug degrades Hsp83 mRNA during the bulk cytoplasm in the embryo although transcripts on the posterior in the embryo are protected. This degradation safety mec hanism thus outcomes in the localization of Hsp83 mRNA towards the posterior with the embryo.