The Role of RNA in Biological Phase Separations - PubMed (original) (raw)

Review

The Role of RNA in Biological Phase Separations

Marta M Fay et al. J Mol Biol. 2018.

Abstract

Phase transitions that alter the physical state of ribonucleoprotein particles contribute to the spacial and temporal organization of the densely packed intracellular environment. This allows cells to organize biologically coupled processes as well as respond to environmental stimuli. RNA plays a key role in phase separation events that modulate various aspects of RNA metabolism. Here, we review the role that RNA plays in ribonucleoprotein phase separations.

Keywords: RNA; membraneless organelle; phase separation.

Copyright © 2018 Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1. Membraneless organelles (MLOs)

Nuclear membraneless organelles include the nucleolus, paraspeckles, nuclear speckles and Cajal bodies. Cytoplasmic membraneless organelles including stress granules and processing bodies. * denotes that these values are reported for treatment with 0.5 mM sodium arsenite for 30 minutes, size of SGs can greatly change with time and stress used.

Figure 2

Figure 2. Paraspeckle Core-Shell Structure

The lncRNA NEAT1.2 (grey lines) acts as structural scaffold, organizing the paraspeckle core (dark grey) around its central region and the shell around its 5’ and 3’ termini. Paraspeckles are further held together by patches (blue) of LCD containing proteins including RBM14 and FUS. NONO, SFPQ and PSPC1, proteins in the DBHS (Drosophila behavior/human splicing) family, as well as FUS make up the core while TDP43 is included in the shell.

Figure 3

Figure 3. Nucleolar processes and structures

The nucleolus is composed of three phase separations that separate the different processes in rRNA production and maturation and are structured around rDNA. Fibrillar center (light orange) is where rDNA is transcribed into rRNA, dense fibril component (orange) where rRNA is processed, granular component (yellow) where rRNA is further processed and assembled into pre-40S (blue oval) and pre-60S (green oval) ribosomal subunits with ribosomal proteins (blue and green shapes).

Figure 4

Figure 4. Stress granule assembly

Stress granules assembly requires two steps: (1) A block in translation initiation that is caused by eIF2α phosphorylation (denoted P) or modulation of the eIF4F complex (denoted with grey lines). This leads to ribosome run-off and an increase in mRNAs with translation initiation stalled 48S complexes. (2) Condensation of these translation initiation stalled mRNAs is then mediated by G3BP1. Other RNA binding proteins and LCD containing proteins are further recruited including signaling molecules.

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