Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs RNA
Impact Factor: 5.844

Membraneless nuclear organelles and the search for phases within phases

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Cells are segregated into two distinct compartment groups to optimize cellular function. The first is characterized by lipid membranes that encapsulate specific regions and regulate macromolecular flux. The second, known collectively as membraneless organelles (MLOs), lacks defining lipid membranes and exhibits self‐organizing properties. MLOs are enriched with specific RNAs and proteins that catalyze essential cellular processes. A prominent sub‐class of MLOs are known as nuclear bodies, which includes nucleoli, paraspeckles, and other droplets. These microenvironments contain specific RNAs, exhibit archetypal liquid–liquid phase separation characteristics, and harbor intrinsically disordered, multivalent hub proteins. We present an analysis of nuclear body protein disorder that suggests MLO proteomes are significantly more disordered than structured cellular features. We also outline common MLO ultrastructural features, exemplified by the three sub‐compartments present inside the nucleolus. A core‐shell configuration, or phase within a phase, is displayed by several nuclear bodies and may be functionally important. Finally, we summarize evidence indicating extensive RNA and protein sharing between distinct nuclear bodies, suggesting functional cooperation and similar nucleation principles. Considering the substantial accumulation of specific coding and noncoding RNA classes inside MLOs, evidence that RNA buffers specific phase transition events, and the absence of a clear correlation between total intrinsic protein disorder and MLO accumulation, we conclude that RNA biogenesis may play a key role in MLO formation, internal organization, and function.

This article is categorized under:

  • RNA Export and Localization > RNA Localization
  • RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
A simplified self‐organizing biological system model. Components (gray/green circles) in a solution are completely intermixed (left) but enter distinct phases upon the introduction of a third component or a change in component state (red circles). Component (e.g., protein) state changes can include posttranslational modifications, such as phosphorylation, acetylation, or methylation. Additional components can include nucleating coding and noncoding RNAs or DNA segment or locus. In biological systems, components sample and reside throughout the system but are enriched in a specific phase, which is represented by the presence of green circles in the gray phase and vice versa
[ Normal View | Magnified View ]
Component miscibility dictates the interaction behavior of self‐organizing droplets. Protein–RNA compartments can form and nucleate into a variety of interaction states. Compartments can convert between different states, depending on protein miscibility, which is in part dictated by electrostatic interactions, multivalency, disorder, and protein/RNA component availability. Any state can be considered either transitional or stable for a given self‐organizing droplet
[ Normal View | Magnified View ]
Intra‐ and inter‐nuclear body noncoding RNA localization. Network chart depicting the number of noncoding RNAs (ncRNAs) that are reported to localize to different nuclear bodies. Connecting nodes represent the number of ncRNAs that exist in both connected nuclear bodies. Table S2 contains the complete list of ncRNAs used to make this chart
[ Normal View | Magnified View ]
Intra‐ and inter‐nuclear body protein localization. Network chart depicting the number of proteins that are reported to localize to different nuclear bodies. Nodes represent the number of proteins that exist in both connected nuclear bodies. Table S2 contains the complete list of proteins used to make this chart
[ Normal View | Magnified View ]
A simplified model of sub‐phase formation. (a) Initial self‐organization occurs as outlined in Figure (single phase to two phases transition). However, green and purple molecules favor interaction with each other but not gray leading to the creation of two compartments. Component miscibility favors formation of a third compartment that is miscible inside the green/purple region but not the gray compartment. This may arise due to existing electrostatic interactions, or a state change such as the introduction of a fourth component or chemical modification. (b) Paraspeckle sub‐phase formation. HAP1 cells were fixed using paraformaldehyde and probed for the NEAT1 lncRNA 5′ end and middle regions to visualize the paraspeckle outer shell and inner core, respectively. (c) Paraspeckle structure in mouse corpus luteal cells. Images kindly supplied by Professors Tetsuro Hirose and Shinichi Nakagawa (both Hokkaido University). The full SRM protocol used to acquire these images is described in West et al. ()
[ Normal View | Magnified View ]
Membraneless organelle proteins exhibit a wide range of IDR content. Validated lists of nuclear body proteins were analyzed using the PONDR‐VLXT algorithm to predict protein disorder. These were plotted alongside the proteasome and nuclear pore complex proteomes, which represent cellular structures that assemble to highly organized structures. Boxplots show the distribution of total disorder percentages for nuclear body component proteins. Boxes display the median, 25th, and 75th percentiles, and whiskers extend to a maximum of 1.5 times the interquartile range. Notches represent 95% confidence intervals on the median. Each dot represents one protein
[ Normal View | Magnified View ]
Membraneless organelles are self‐organizing droplets that are present in the cell nucleus. (a) Human aneuploid HeLa cells transiently overexpressing the nucleolar (“No”) methyltransferase fibrillarin fused to green fluorescent protein (GFP) were fixed with 4% paraformaldehyde for 10 min, washed with PBS, permeabilized with 0.2% triton X‐100, and subjected to indirect immunostaining to visualize nuclear speckles (p‐SRSF2, red, “S”) and RNA FISH to visualize paraspeckles (NEAT1 lncRNA, white, “P”). Nuclei borders are false‐annotated using a white dashed line. Scale bar = 2 μm. (b) Transient expression of fibrillarin‐GFP and RFP‐tagged RNA polymerase I subunit RPA43, combined with immunostaining for nucleophosmin, a major nucleolar chaperone, reveals that the nucleolus is comprised of three distinct but interacting functional compartments that reflect the movement of pre‐ribosomal particles away from rDNA transcription sites to the granular component
[ Normal View | Magnified View ]

Browse by Topic

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Export and Localization > RNA Localization

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts