Spatial and temporal control of RNA stability.

Maternally encoded RNAs and proteins program the early development of all animals. A subset of the maternal transcripts is eliminated from the embryo before the midblastula transition. In certain cases, transcripts are protected from degradation in a subregion of the embryonic cytoplasm, thus resulting in transcript localization. Maternal factors are sufficient for both the degradation and protection components of transcript localization. Cis-acting elements in the RNAs convert transcripts progressively (i) from inherently stable to unstable and (ii) from uniformly degraded to locally protected. Similar mechanisms are likely to act later in development to restrict certain classes of transcripts to particular cell types within somatic cell lineages. Functions of transcript degradation and protection are discussed.

RNA localization and translational regulation during axis specification in the Drosophila oocyte.

The major axes of the oocyte-antero-posterior and dorso-ventral-are established over a one-day period during mid-oogenesis in Drosophila. The same molecule, GURKEN (GRK), functions to initiate signaling between the oocyte and the surrounding, somatically derived follicle cells. This results first in specification of the antero-posterior axis and, later, the dorso-ventral axis of the oocyte and surrounding follicle cells. Central to specification of both axes is a combination of cytoplasmic localization and translational regulation of the grk RNA. Here we discuss the mechanisms by which the grk RNA is localized within the oocyte and the role of translational regulation in spatially restricting the production of GRK protein. We then discuss the generality of these mechanisms during oogenesis by focusing on a second transcript, oskar, whose function is also regulated through a combination of transcript localization and translational control.

Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster.

Maternally synthesized RNAs program early embryonic development in many animals. These RNAs are degraded rapidly by the midblastula transition (MBT), allowing genetic control of development to pass to zygotically synthesized transcripts. Here we show that in the early embryo of Drosophila melanogaster, there are two independent RNA degradation pathways, either of which is sufficient for transcript elimination. However, only the concerted action of both pathways leads to elimination of transcripts with the correct timing, at the MBT. The first pathway is maternally encoded, is targeted to specific classes of mRNAs through cis-acting elements in the 3'-untranslated region and is conserved in Xenopus laevis. The second pathway is activated 2 h after fertilization and functions together with the maternal pathway to ensure that transcripts are degraded by the MBT.

RNA localization in development.

Cytoplasmic RNA localization is an evolutionarily ancient mechanism for producing cellular asymmetries. This review considers RNA localization in the context of animal development. Both mRNAs and non-protein-coding RNAs are localized in Drosophila, Xenopus, ascidian, zebrafish, and echinoderm oocytes and embryos, as well as in a variety of developing and differentiated polarized cells from yeast to mammals. Mechanisms used to transport and anchor RNAs in the cytoplasm include vectorial transport out of the nucleus, directed cytoplasmic transport in association with the cytoskeleton, and local entrapment at particular cytoplasmic sites. The majority of localized RNAs are targeted to particular cytoplasmic regions by cis-acting RNA elements; in mRNAs these are almost always in the 3'-untranslated region (UTR). A variety of trans-acting factors--many of them RNA-binding proteins--function in localization. Developmental functions of RNA localization have been defined in Xenopus, Drosophila, and Saccharomyces cerevisiae. In Drosophila, localized RNAs program the antero-posterior and dorso-ventral axes of the oocyte and embryo. In Xenopus, localized RNAs may function in mesoderm induction as well as in dorso-ventral axis specification. Localized RNAs also program asymmetric cell fates during Drosophila neurogenesis and yeast budding.