Molecular motors: directing traffic during RNA localization

Abstract

RNA localization, the enrichment of RNA in a specific subcellular region, is a mechanism for the establishment and maintenance of cellular polarity in a variety of systems. Ultimately, this results in a universal method for spatially restricting gene expression. Although the consequences of RNA localization are well-appreciated, many of the mechanisms that are responsible for carrying out polarized transport remain elusive. Several recent studies have illuminated the roles that molecular motor proteins play in the process of RNA localization. These studies have revealed complex mechanisms in which the coordinated action of one or more motor proteins can act at different points in the localization process to direct RNAs to their final destination. In this review, we discuss recent findings from several different systems in an effort to clarify pathways and mechanisms that control the directed movement of RNA.

Figure 1. Examples of RNA Localization

(A) β-actin mRNA(red stipples)is localized to the leading edge of chick embryo fibroblasts by a myosin Vmotor. (B)Localization of RNAs in the Drosophila oocyte. Oskar mRNA (green stipples) is transported to the posterior pole of oocyte by kinesin-1. Bicoid mRNA (red stipples) is transported to the anterior of the oocyte by dynein. Dynein also localizes gurken mRNA (black stipples) to the dorso-anterior corner of the oocyte. (C) Vg1 mRNA (red stipples) is transported to the vegetal pole of the Xenopus oocyte by kinesin-1 and kinesin-2. (D) Localization of ASH1 mRNA (red stipples) to the daughter cell in budding yeast is mediated by a myosin motor. (E) Localization of the pair-rule mRNAs (red stipples) to the apical side of nuclei in the Drosophila syncytial blastoderm embryo mediated by dynein. (F) mRNAs localized to growth cones and dendrites of neurons mediated by kinesin. For all panels, nuclei are shown in gray. A color version of this figure is available online.

Figure 2. Molecular Motors

Cargo domains are labeled in orange, microtubule binding domains in green, and actin binding domains in purple. Some subunits have been omitted for clarity. (A) Dimeric myosin-V. (B) Heterotetrameric kinesin-1. Kinesin Heavy Chains (KHC) and Kinesin Light Chains (KLC) are indicated. (C) Heterotrimeric kinesin-2. The motor domain-containing heavy chains, Klp3a and Klp3b are indicated, as is the cargo-binding Kinesin Associated Protein (KAP). (D) Cytoplasmic dynein. Dynein Heavy Chains (DHC), Dynein Light Intermediate Chains (DLIC), Dynein Intermediate Chains (DIC) and Dynein Light Chains (DLC) are indicated. (E) The multi-subunit dynactin complex. p150^Glued, dynamitin and Arp1 subunits are indicated. A color version of this figure is available online.

Figure 3. Links Between Localized RNAs and Molecular Motors

(A) The ASH1 mRNA localization complex in budding yeast. Elements in the ASH1 mRNA are recognized by the RNA-binding protein She2p. She3p functions as an adapter by binding both Myo4p and She2p to connect ASH1 mRNA to the myosin motor for transport to the barbed ends of actin microfilaments. (B) Localization of pair-rule mRNAs in Drosophila. Egalitarian (Egl) recognizes RNA motifs in the 3′ UTR of pair-rule mRNAs and is bound by BicaudalD (BicD). Both Egl and BicD interact with the dynein motor, via the DLC and DIC, respectively. Dynein acts to transport the RNP cargo to the minus ends of microtubules. (C) Suggested interactions with FMRP target RNAs. RNAs recognized by the RNA-binding protein FMRP may be coupled to dynein and kinesin motors either directly, or indirectly through the adapter protein BicD, for transport on microtubules. Dynactin is omitted from this figure for simplicity. A color version of this figure is available online.