mRNA localization and translational control in Drosophila oogenesis

Abstract

Localization of an mRNA species to a particular subcellular region can complement translational control mechanisms to produce a restricted spatial distribution of the protein it encodes. mRNA localization has been studied most in asymmetric cells such as budding yeast, early embryos, and neurons, but the process is likely to be more widespread. This article reviews the current state of knowledge about the mechanisms of mRNA localization and its functions in early embryonic development, focusing on Drosophila where the relevant knowledge is most advanced. Links between mRNA localization and translational control mechanisms also are examined.

Figure 1.

Localization of patterning mRNAs in Drosophila oogenesis. (A) In early oogenesis, several mRNAs, including grk, nos, osk, and bcd, are transported from the nurse cells through cytoplasmic bridges called ring canals into the oocyte. This involves minus-end directed transport along microtubules (blue arrows) mediated by the dynein motor complex. Abbreviations: nc, nurse cells, fc, follicle cells, oo, oocyte. (B) In mid-oogenesis, osk mRNA localizes to the posterior of the oocyte, grk mRNA localizes to the anterodorsal corner in close association with the oocyte nucleus, and bcd mRNA localizes to the anterior pole. (C) In late oogenesis, centrifugal cytoplasmic streaming (delineated by arrows) coupled with posterior anchoring brings about a further posterior enrichment of osk mRNA as well as posterior enrichment of nos mRNA. The distribution of bcd mRNA at the anterior pole is further refined.

Figure 2.

Model for linking mRNAs to the microtubule cytoskeleton for minus-end directed transport. Egalitarian (Egl) interacts directly with localization signals on mRNAs, with the carboxy-terminal end of Bicaudal-D (Bic-D), and with dynein light chain (Dlc). Bic-D interacts directly with dynactin, which in turn binds to dynein through its intermediate chain (Dic). Dynein heavy chain (Dhc) interacts with microtubules (green arrow) and catalyzes movement toward the minus-end. Although both in vivo and in vitro evidence exists to support this model for some instances of dynein-directed minus-end transport, and Egl and Bic-D are required for accumulation of grk, nos, osk, and bcd mRNAs into the oocyte, it has not yet been directly shown that this mechanism governs this particular localization event.

Figure 3.

Mechanisms of establishing protein gradients in the early embryo prior to the onset of zygotic transcription. (A) Maternally expressed bcd mRNA (top panel) is localized in a steep gradient at the anterior pole. Bcd protein (lower panel) is translated from that localized mRNA and diffuses toward the posterior. (B) Maternally-expressed cad mRNA (top panel) is uniformly distributed. Translation of cad mRNA is, however, repressed by Bcd-mediated recruitment of 4EHP, resulting in a posterior-to-anterior gradient of Cad protein (lower panel) that is a mirror image of the Bcd gradient. (C) Maternally expressed hb mRNA (top panel) is uniformly distributed. Translation of hb mRNA is repressed by a complex of Nos, Pum, and Brat, that recruits 4EHP and probably other negative regulators to restrict Hb protein (lower panel) to the anterior half of the embryo. (D) Maternally expressed nos mRNA (top panel) is enriched at the posterior pole but present elsewhere. Translation of nos outside the posterior is repressed by Smg, which can recruit the repressor protein Cup and also the CCR4 deadenylase complex. Unlocalized nos is also targeted by piRNAs (not shown). Nos protein (lower panel) is translated from posteriorly-localized nos that is protected from degradation and repression.