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Abstract:

The dynamic formation of stress granules (SGs), processing bodies (PBs), and related RNA organelles regulates diverse cellular processes, including the coordination of functionally connected messengers, the translational regulation at the synapse, and the control of viruses and retrotransposons. Recent studies have shown that pyruvate kinase and other enzymes localize in SGs and PBs, where they become protected from stress insults. These observations may have implications for enzyme regulation and metabolic control exerted by RNA-based organelles. The formation of these cellular bodies is governed by liquid-liquid phase separation (LLPS) processes, and it needs to be strictly controlled to prevent pathogenic aggregation. The intracellular concentration of key metabolites, such as ATP and sterol derivatives, may influence protein solubility, thus affecting the dynamics of liquid organelles. LLPS in vitro depends on the thermal diffusion of macromolecules, which is limited inside cells, where the condensation and dissolution of membrane-less organelles are helped by energy-driven processes. The active transport by the retrograde motor dynein helps SG assembly, whereas the anterograde motor kinesin mediates SG dissolution; a tug of war between these two molecular motors allows transient SG formation. There is evidence that the efficiency of dynein-mediated transport increases with the number of motor molecules associated with the cargo. The dynein-dependent transport may be influenced by cargo size as larger cargos can load a larger number of motors. We propose a model based on this emergent property of dynein motors, which would be collectively stronger during SG condensation and weaker during SG breakdown, thus allowing kinesin-mediated dispersion. © 2018 American Chemical Society.

Registro:

Documento: Artículo
Título:Life and Work of Stress Granules and Processing Bodies: New Insights into Their Formation and Function
Autor:Perez-Pepe, M.; Fernández-Alvarez, A.J.; Boccaccio, G.L.
Filiación:Instituto Leloir, IIBBA-CONICET, Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, Instituto de Investigaciones Bioquĺmicas de Buenos Aires (IIBBA), Buenos Aires, Argentina
Palabras clave:Condensation; Dissolution; Enzymes; Granulation; Liquids; Phase separation; RNA; Viruses; Cellular process; Emergent property; Enzyme regulation; Intracellular concentration; Liquid-liquid phase separation; Metabolic control; Protein solubility; Translational regulation; Freight transportation; adenosine triphosphate; dynein adenosine triphosphatase; kinesin; messenger RNA; molecular motor; RNA; RNA binding protein; sterol derivative; transcriptome; adenosine triphosphate; dynein adenosine triphosphatase; kinesin; pyruvate kinase; RNA; cell function; cell granule; cell growth; cell metabolism; cell stress; cell structure; concentration (parameters); cytosol; dispersion; dissolution; enzyme regulation; gene function; gene ontology; glycosome; in vitro study; liquid liquid phase separation; liquid phase microextraction; macromolecule; metabolic regulation; metabolite; microtubule; molecular dynamics; nonhuman; phase separation; priority journal; protein analysis; Review; RNA binding; RNA metabolism; solubility; thermal diffusion; cell organelle; chemistry; cytoplasm; genetics; human; membrane; transport at the cellular level; Adenosine Triphosphate; Biological Transport; Cytoplasm; Dyneins; Humans; Kinesin; Membranes; Microtubules; Organelles; Pyruvate Kinase; RNA; Solubility
Año:2018
Volumen:57
Número:17
Página de inicio:2488
Página de fin:2498
DOI: http://dx.doi.org/10.1021/acs.biochem.8b00025
Título revista:Biochemistry
Título revista abreviado:Biochemistry
ISSN:00062960
CODEN:BICHA
CAS:adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; dynein adenosine triphosphatase; RNA, 63231-63-0; pyruvate kinase, 9001-59-6; Adenosine Triphosphate; Dyneins; Kinesin; Pyruvate Kinase; RNA
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v57_n17_p2488_PerezPepe

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Citas:

---------- APA ----------
Perez-Pepe, M., Fernández-Alvarez, A.J. & Boccaccio, G.L. (2018) . Life and Work of Stress Granules and Processing Bodies: New Insights into Their Formation and Function. Biochemistry, 57(17), 2488-2498.
http://dx.doi.org/10.1021/acs.biochem.8b00025
---------- CHICAGO ----------
Perez-Pepe, M., Fernández-Alvarez, A.J., Boccaccio, G.L. "Life and Work of Stress Granules and Processing Bodies: New Insights into Their Formation and Function" . Biochemistry 57, no. 17 (2018) : 2488-2498.
http://dx.doi.org/10.1021/acs.biochem.8b00025
---------- MLA ----------
Perez-Pepe, M., Fernández-Alvarez, A.J., Boccaccio, G.L. "Life and Work of Stress Granules and Processing Bodies: New Insights into Their Formation and Function" . Biochemistry, vol. 57, no. 17, 2018, pp. 2488-2498.
http://dx.doi.org/10.1021/acs.biochem.8b00025
---------- VANCOUVER ----------
Perez-Pepe, M., Fernández-Alvarez, A.J., Boccaccio, G.L. Life and Work of Stress Granules and Processing Bodies: New Insights into Their Formation and Function. Biochemistry. 2018;57(17):2488-2498.
http://dx.doi.org/10.1021/acs.biochem.8b00025