Polarizing genetic information in the egg: RNA localization in the frog oocyte

Abstract

RNA localization is a powerful strategy used by cells to localize proteins to subcellular domains and to control protein synthesis regionally. In germ cells, RNA targeting has profound implications for development, setting up polarities in genetic information that drive cell fate during embryogenesis. The frog oocyte offers a useful system for studying the mechanism of RNA localization. Here, we discuss critically the process of RNA localization during frog oogenesis. Three major pathways have been identified that are temporally and spatially separated in oogenesis. Each pathway uses a different mechanism to effect RNA localization. In some cases, localization elements within the 3' untranslated region have been identified and have provided unique insights into the localization process. This important field is still in its infancy, however, and much remains to be learned. BioEssays 21:546–557, 1999. © 1999 John Wiley & Sons, Inc.

The KH domains of Xenopus Vg1RBP mediate RNA binding and self-association

“…Vg1RBP (also known as Vera) is a protein implicated in localizing Vg1 mRNA to the vegetal cortex during Xenopus oogenesis (Deshler et al+, 1998;Havin et al+, 1998;Zhang et al+, 1999;Kwon et al+, 2002)+ One of the bestcharacterized localized maternal RNAs in Xenopus, Vg1 mRNA encodes a TGF-b-like factor involved in mesoderm induction and left-right axis formation+ Vg1 mRNA translocation to and anchoring at the vegetal cortex involves microtubules and microfilaments, respectively, and is mediated by the 340-nt 39 UTR vegetal localization element (VLE) defined in microinjection assays (Yisraeli et al+, 1990;Mowry & Melton, 1992; reviewed in King et al+, 1999;Palacios & St+ Johnston, 2001;Yaniv & Yisraeli, 2001;Kloc et al+, 2002)+ Vg1 mRNA is not translated until the mRNA is localized, reflecting the tight control of RNA translation and localization shown to be critical for pattern formation in Drosophila (Palacios & St+ Johnston, 2001;Kloc et al+, 2002)+ The 250-nt UA-rich element that represses Vg1 mRNA translation is also located in the 39 UTR, distinct from and downstream of the VLE (Wilhelm et al+, 2000;Otero et al+, 2001)+ Several proteins interact specifically with the VLE (Mowry, 1996), including Vg1RBP/Vera (Deshler et al+, 1998;Havin et al+, 1998;Zhang et al+, 1999), hnRNP I/PTB (Cote et al+, 1999), and PrrP (Zhao et al+, 2001), all of which colocalize with Vg1 mRNA and are thought to play a role in the localization process+ Vg1RBP/Vera and hnRNP I bind the pyrimidine-rich VM1 and E2 motifs which are repeated three to five times throughout the VLE; mutation or deletion of these elements abolishes protein-binding and RNA localization (Deshler et al+, 1998;Havin et al+, 1998;Cote et al+, 1999;Bubunenko et al+, 2002;Kwon et al+, 2002)+ Vg1RBP mediates the association of Vg1 RNA with microtubules in Xenopus oocytes (Elisha et al+, 1995), whereas PrrP has been reported to bind to ligands involved in actin polymerization (Zhao et al+, 2001)+ Although these data strongly implicate these proteins in mediating Vg1 mRNA localization, the actual binding sites of Vg1RBP/ hnRNP I/P...…”

Teachings from the egg: New and unexpected functions of RNAs

“…Its animal hemisphere is devoid of yolk and contains the oocyte nucleus, and the yolky vegetal hemisphere contains various localized mRNAs (such as Bicaudal-C, Fatvg, VegT, Vg1, Wnt11, and Xcat2 mRNAs) whose protein products play a role in endoderm, mesoderm, and germ cell formation (Forristall et al, 1995;Zhang and King, 1996;Chan et al, 1999Chan et al, , 2001Chan et al, , 2007King et al, 1999;Houston and King, 2000;Lipshitz and Smibert, 2000;Wessely and de Roberis, 2000;Heasman et al, 2001;Kloc et al, 2001Kloc et al, , 2002Xanthos et al, 2001). These localized RNAs are anchored at the oocyte vegetal cortex composed of the network of cytokeratin and actin filaments (Elinson et al, 1993;Forristall et al, 1995;Alarcon and Elinson, 2001;Heasman et al, 2001;Kloc et al, 2002Clarke and Allan, 2003).…”

“…These localized RNAs are anchored at the oocyte vegetal cortex composed of the network of cytokeratin and actin filaments (Elinson et al, 1993;Forristall et al, 1995;Alarcon and Elinson, 2001;Heasman et al, 2001;Kloc et al, 2002Clarke and Allan, 2003). The vegetal cortex of the oocyte also anchors the germinal granules, which are a determinant of germ cell fate in the embryo (King et al, 1999;Houston and King, 2000;Kloc et al, 2002.…”

“…The perfect example is the discovery and the studies of the function of localized RNAs. The first localized mRNAs were discovered over 2 decades ago in the oocytes of Drosophila fly and Xenopus frog (Rebagliati et al, 1985;Frigerio et al, 1986); then over 100 different localized RNAs have been found in unicellular organisms and in various cell types of animal and plant species (Bashirullah et al, 1998;King et al, 1999;Lipshitz and Smibert, 2000;Jansen, 2001;Kloc et al, 2001Kloc et al, , 2002Zhou and King, 2004;.…”

“…The simplest and most widely accepted explanations for the biological function of mRNA localization phenomenon include: (1) to assure the high-level synthesis of protein encoded by localized mRNA at the site where it is needed the most and (2) to prevent the protein from being synthesized in the region of the cell where it is not needed or could have a harmful effect (Bashirullah et al, 1998;King et al, 1999;Lipshitz and Smibert, 2000;Jansen, 2001;Kloc et al, 2002). Thus, the assumption has always been that the only function of mRNA (localized and unlocalized) is to make a protein.…”