RNA localization regulates diverse and dynamic cellular processes

Abstract

At the nexus of specialized cellular responses are localized enrichments of protein activity. The localization of messenger RNA (mRNA) coupled with translational control often plays a crucial role in the generation of protein concentrations at defined subcellular domains. Although mRNA localization is classically associated with large specialized cells, such as neurons and embryos, RNA localization is a highly conserved paradigm of post-transcriptional regulation observed in diverse cellular contexts. Functions of localized mRNAs extend far beyond the well-studied examples of neuronal polarization and developmental patterning. Since the initial discovery of the intracellular localization of cytoskeletal mRNAs within migrating cells, hundreds of mRNAs are now known to be enriched at specific organelles where they contribute to cell function. In this short review, we discuss basic principles regulating RNA localization and consider the contribution of localized mRNA to several essential cellular behaviors. We consider RNA localization as a mechanism with widespread implications for cellular function.

Keywords: RNA localization; RNA-binding proteins; centrosomes; endoplasmic reticulum; focal adhesions; mitochondria; translational control.

Figure 1. RNA localization within polarized cells

(A) Multiple mRNAs (colored sinusoidal lines) localize to neuronal processes and contribute to neuronal polarization and function. (B) In migrating fibroblasts, β-actin mRNA (red) localizes to the leading edge of cells and to FA plaques (grey ovals), while vimentin mRNA (brown) is enriched at the perinuclear domain. β-actin localization and translation at focal adhesions contributes to the regulation of adhesion and migration. (C) In epithelial cells, β-actin and E-cadherin mRNAs localize to adherens junctions, whereas zonula occludens-1 mRNA (ZO-1) localizes to tight junctions to regulate cell adhesion.

Figure 2. Proposed roles of mRNA localized to centrosomes

While the exact function of mRNA localized to centrosomes remains unknown, several models have been proposed. Note that these models of RNA function at centrosomes are non-exclusive. (A) RNA localization to centrosomes may regulate centrosome biology through translational regulation. Centrosome localization may represent a translationally permissive or inhibitory environment. Alternatively, RNA localization may sequester transcripts away from the cytosolic translational machinery. (B) RNA localization may contribute to centrosome structure, such as through the formation of a phase separated condensate. (C) The asymmetric distribution of centrosome-localized RNAs may regulate asymmetric cell divisions.