RNA Granules and Membraneless Organelles
المؤلف:
Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.
المصدر:
Hematology : Basic Principles and Practice
الجزء والصفحة:
8th E , P40
2025-05-28
584
In the nucleus and in the cytoplasm, RNA availability and fate are additionally controlled by their localization in so-called RNA granules, liquid droplets, or membraneless organelles; within the same organelles, RNA may exert regulatory control on the function and availability of proteins and RNA-protein complexes.[1] Within the cell such organelles exist in the nucleus, such as nucleoli, Cajal bodies, nuclear speckles, and paraspeckles. In the cytoplasm, they exist in the form of processing (P) bodies, stress granules, and germ granules (Table 1). Liquid droplet organelles are formed by LLPS similar to the separation of oil and vinegar in vinaigrette. They function as organizational tools by concentrating cellular components in membraneless structures that allow rapid exchange of their components unhindered by membrane barriers. Their “fluidity,” for most components’ residence times, ranges from seconds to tens of seconds and allows for dynamic finetuning of biochemical reactions and rapid response to cellular stress. In general, liquid droplet organelles are made up of RNA and RNA-binding proteins. As an example, Cajal bodies in the nucleus form on active snRNA loci and are the site of snRNA processing and snRNP assembly and surveillance. Nucleoli regulate rRNA synthesis and are known to capture and detain proteins via lncRNA binding. Nuclear speckles and paraspeckles form on the two long ncRNAs MALAT1 and NEAT1, respectively, and contain mRNAs and their RNA-binding proteins. Nuclear speckles are the sites of RNA splicing. Paraspeckles sequester proteins and RNAs in response to cellular stress. Stress granules and P-bodies in the cytoplasm regulate RNA stability and protein translation. RNA is sequestered in stress granules in response to stress signals, hypothesized to regulate translation, RNA stability, and cell survival; in P-bodies, translation is stalled and transcripts are targeted for degradation by exonucleases.
Table1. RNA Granules
The study of LLPS and the function of liquid droplet organelles in vivo and their role in physiologic responses and disease are an ongoing subject of intense studies.[2] Aberrant phase transitions from a liquid state to a more aggregated state have been recognized as the causal mechanism in neurodegenerative disorders (e.g. via mutations in the RNA-binding proteins usually part of stress granules that render the proteins more likely to aggregate) and cancers.
References
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[1] Tian S, Curnutte HA, Trcek T. RNA granules: a view from the RNA perspective. Molecules. 2020;25(14):3130.
[2] Corbet GA, Parker R. RNP granule formation: lessons from P-bodies and stress granules. Cold Spring Harb Symp Quant Biol. 2019;84:203–215.
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