Subcellular mRNA localization in animal cells and why it matters

Abstract

Subcellular localization of messenger RNAs (mRNAs) can give precise control over where protein products are synthesized and operate. However, just 10 years ago many in the broader cell biology community would have considered this a specialized mechanism restricted to a very small fraction of transcripts. Since then, it has become clear that subcellular targeting of mRNAs is prevalent, and there is mounting evidence for central roles for this process in many cellular events. Here, we review current knowledge of the mechanisms and functions of mRNA localization in animal cells.

Fig. 1

mRNA localization is a multi-step process. Shown is an illustration of two stylized cells, depicting mechanisms that can contribute to mRNA localization. (A) Protection of mRNAs from degradation. Red, nuclear RNA recognition factor; dark blue, cytoplasmic RNA recognition factor; yellow, ribonuclease; purple, agonist of degradation. (B) Motor-based transport. Green, nuclear RNA recognition factor; light blue and light gray, cytoplasmic RNA recognition factor; red and purple, molecular motors; orange, anchorage factor. In reality, different combinations of these mechanisms may be used to localize a single mRNA species in the same cell.

Fig. 2

Examples of asymmetrically localized mRNAs. (A) Differential localization of mRNA determinants within the Drosophila oocyte. (B) Animal localization of a transcript encoding a signaling molecule required for axis development in the egg of a cnidarian, Clytia. (C) mRNA enrichment in synapses of an Aplysia sensory neuron in response to contact with a target motor neuron (blue). (D) Apical localization of an mRNA in the Drosophila embryo, which facilitates entry of its transcription factor product into the nuclei (purple). (E) mRNA localization in pseudopodial protrusions of a cultured mammalian fibroblast (red signal indicates the cell volume). (F) mRNA enrichment within a Xenopus axonal growth cone. mRNAs were visualized by means of in situ hybridization except in (E), in which the MS2–green fluorescent protein (GFP) system was used. Drosophila images are reproduced from (50) with permission. [Images were kindly provided by (B) T. Momose and E. Houliston, (C) D.O. Wang and K. Martin, (D) M. Dienstbier, (E) S. Mili and I. Macara, and (F) F. van Horck.]

Fig. 3

Extrinsic stimuli elicit changes in subcellular mRNA localization and translation. (A) A polarizing stimulus elicits asymmetric localization and translation of mRNAs encoding β-actin and actin regulators on the near-stimulus side of the leading edge of migrating cells, such as fibroblasts and axonal growth cones, thus contributing to polarized cell movement and directional steering. The dashed outline denotes the post-stimulus trajectory. (B) Electrical input from presynaptic contacts selectively induces localized trafficking and translation of specific mRNAs in dendrites that mediate changes in spine morphology (dashed outline) and plasticity. Several aspects of these models are speculative.