Mechanisms and consequences of subcellular RNA localization across diverse cell types

Abstract

Essentially all cells contain a variety of spatially restricted regions that are important for carrying out specialized functions. Often, these regions contain specialized transcriptomes that facilitate these functions by providing transcripts for localized translation. These transcripts play a functional role in maintaining cell physiology by enabling a quick response to changes in the cellular environment. Here, we review how RNA molecules are trafficked within cells, with a focus on the subcellular locations to which they are trafficked, mechanisms that regulate their transport and clinical disorders associated with misregulation of the process.

Keywords: RNA binding protein; RNA cis-element; RNA localization; RNA transport; zipcode.

Figure 1:. Mechanisms of RNA localization.

A) Local RNA transcriptomes are established in neurons to facilitate local protein production in response to stimuli. RNA binding proteins are essential for transport of these RNAs. B) RNAs are transported along cytoskeletal networks in various cell types. Short range transport is typically mediated by actin filaments and myosins, which can facilitate retrograde and anterograde movement. Long range transport is achieved with microtubules in both retrograde and anterograde movement using dynein and kinesin, respectively. C) Concentration gradients of RNAs are established using anchors composed of proteins that sequester RNA.

Figure 2:. Misregulation of RNA localization is relevant to disease phenotypes.

A) RNA localization patterns to various subcellular compartments are disrupted in various diseases. B) Establishment of EMT is associated with RNA localization changes. C) Gradients of RNA concentrations are observed between the apical and basal axis of epithelial cells; however, it is not clear if disruption of these patterns contributes to disease phenotypes. D) Asymmetric distribution of RNAs helps establish developmental states and disruption of these patterns contributes to establishment of cancer.