Taking a cellular road-trip: mRNA transport and anchoring

Abstract

mRNA localization is a crucial mechanism for post-transcriptional control of gene expression used in numerous cellular contexts to generate asymmetric enrichment of an encoded protein. This process has emerged as a fundamental regulatory mechanism that operates in a wide range of organisms to control an array of cellular processes. Recently, significant advances have been made in our understanding of the mechanisms that regulate several steps in the mRNA localization pathway. Here we discuss the progress made in understanding localization element recognition, paying particular attention to the role of RNA structure. We also consider the function of mRNP granules in mRNA transport, as well as new results pointing to roles for the endocytic pathway in mRNA localization.

Figure 1. mRNA localization in Drosophila oocytes and embryos, and animal neurons

A. K10 mRNA (magenta) localizes to the anterior and oskar mRNA to the posterior (purple) of a developing Drosophila oocyte. The oocyte is depicted on the right, surrounded by somatic follicle cells. B. bicoid mRNA (blue) localizes to the anterior and oskar (purple) mRNA to the posterior of the Drosophila egg. C. K10 mRNA (magenta) is found at the apical side of the blastoderm nuclei (black), which are partially separated from one another by invaginated cell membranes. D. Nanos (red) and Vg1 (pale blue) localize to the vegtal pole of the Xenopus oocyte utilizing two alternative localization pathways referred to as the early (active in stages I and II of oogenesis) and late (active in stages II–IV) pathways, respectively. The oocyte depicted is in stage IV of oogenesis. E. ASH1 mRNA (green) localizes to the distal tip of a budding daughter cell during mitosis in the yeast Saccharomyces cerevisiae. F. β-actin mRNA (orange) localizes to the leading edge of motile fibroblast. G. CamKIIα mRNA (yellow) localizes to the dendrites of a neuron, whereas PSD-95 mRNA (pale green) is found at the post-synaptic side of a synapse.

Figure 2. Structural motifs involved in mRNA localization

A. Secondary structure of the K-10 LE. The three helical sections of the hairpin are shown with colored base-pairs (proximal blue, medial green, and distal pink). A flipped out U is present in the loop. This structural representation is based upon Figure 1 of [30••]. B. Depiction of A-form RNA, A′-form RNA, and B-form DNA helices. The K-10 LE stem folds into A′-form helices, in which the size of the major groove is similar to that of B-form DNA. This is in contrast to the small major groove found in the more common A-form RNA helix. This image is again based upon Figure 1 of [30••]. C. The SOLE is formed after splicing of the first intron in osk pre-mRNA [32••]. Exon 1 is shown as pink and exon 2 is green in both the pre-mRNA (top) and the spliced product (below). The inset shows the exon 1 (pink) and exon 2 (green) sequences within the SOLE and the position of the EJC (open arrowhead), 20–24nts upstream of the splice junction (filled arrowhead). D. The oskar SOLE is predicted to form a hairpin, with the proximal and distal stems shown with blue and green basepairs, respectively. E. Secondary structure of the CamKIIα LE in mammals, as depicted in [37•]. F. CamKIIα LE folds into a G-quadruplex through hydrogen-bond interactions indicated by dashed lines.