The initiation of translation is hampered under stressed conditions. As a result, P bodies and stress granules (SGs) are formed. These granules control the fate of messenger RNA (mRNA).
Processing (P) bodies and their components (mRNA and mRNA decay machinery) act as sites where mRNA are degraded. On the other hand, stress granules are made of substances that initiate translation as well as eukaryotic small ribosomal subunits and thus hypothesized to play a fundamental role in translating particular mRNAs needed for stress adaptation. Recent research studies have also found out that yeast contains SGs or EGP bodies that are thought to protect the cells from dying when under ethanol stress.
TORC1 in S. cerevisiae revealed that overexpression of Pbp1 downregulates TORC1 by stimulating the formation of SG, where TORC1 is recruited. More significantly, TORC1 is sequestered into SGs in the presence of heat stress, a physiological SG-stimulating condition. These results imply that SGs act to sequester TORC1 in the presence of heat stress.
In the presence of environmental stress, cell respond by downregulating energy-demanding processes and inhibiting growth. Studies have shown that TOR plays a role in the stress response. For instance, in hypoxia, there is inhibition of TOR signaling and protein synthesis is thus downregulated
Apart from enhancing metabolic processes, TORC1 plays a vital role in stopping responses to stress. It has also been found to enhance growth by inhibiting many stress-response programs. Even though it is critical for survival under environmental stress, TORC1 activation of pathways that respond to stress decreases growth rates and may result in cell death.
Cell wall integrity pathway: In yeast cells, the cell walls are vital for survival in harsh environments. Moreover, cell walls protect the cell membrane from bursting by preventing internal turgor pressure. Even though thickened cell wall is essential for the protection of stationary-phase cells, the rigid cell wall must be remodeled to provide room for cell growth. Activation of the pathway results in the expression of various enzymes which play a role in cell wall synthesis. These enzymes help restructure the cell wall in times of normal growth as well as in response to stress.
TORC1 accelerates cell growth: Under optimum environmental conditions, TORC1 is involved in the coordination of production and growth of cellular mass.
The stress response in eukaryotic cells has been found to inhibit the initiation of translation and result in the formation of cytoplasmic RNA-protein complexes known as SGs. SGs have nontranslating mRNAs and various additional proteins which affect mRNA function. SGs have been hypothesized to affect mRNA translation as well as its stability and have been associated with apoptosis and nuclear processes. Moreover, SGs interact with P-bodies, translation repressors, and certain mRNA degradation molecules. Both SGs and P-bodies have shown a dynamic cycle of unique biochemical and compartmentalized mRNPs in the cytosol, which has effects on the regulation of mRNA function.
The biological goal of the stress response is to protect cell constituents against the potentially harmful effects of current stress factors and also prepare the cells against future detrimental environmental factors of similar or a different kind.
P-bodies are RNA-protein granules that have untranslating mRNAs with a group of translation repressors, the mRNA decapping molecules, and the 53 exonuclease Xrn1. The P bodies are found in plants, mammalian cells, and yeast cells.
Processing bodies have been found to play a role in mRNA decapping.
The yeast homolog of Pub1, TIA-1, enhances stress granule build-up with the help of glutamine-rich prion regions
Orthologues of Pub1 and Pbp1 have an impact on the assembly of SGs in mammalian cells.
The Saccharomyces cerevisiae Pbp1 is thought to play a vital role in RNA metabolism and control of translation because Pbp1 determines the length of the poly(A) tail and also helps in the formation of SGs. However, the physiological role of Pbp1is still not clear since its mutation has no direct effect on cell growth.
Akahara and Maedas argued that sequestration of TORC1 in SGs inhibit the functional capacity of TORC1. They proved this as follows: First, they demonstrated Kog1 and Tor1 localization in SGs and its coimmunoprecipitation with Pbp1. They also showed that Pbp1 capacity to downregulate TOR cell signal pathway, coimmunoprecipitate with a target of rapamycin complex 1 (TORC1), and put TORC1 into SGs is affected by Pbp1s capacity to self-associate, which is also important for localization of Pbp1 within and accelerating build-up of SGs. Lastly, the kinetic analysis revealed that the rejuvenation of TOR signaling after the stress is positively associated with its exit from SGs, while genetic and chemical factors that change SGs production are also positively related to TOR signaling activity. Akahara and Maedas model explains that the first role of stress is its inactivation of TOR and blocking of translation, which enhances SG formation and sequestration of certain TORC1 molecules. After sequestration, TORC1 is reduced in its functioning until the stress is lessened.
The stability of mRNA is regulated by molecules in the mRNA transcript as well as their cognate RNA-binding proteins. Pub1 is mRNA found in the cytoplasm of Saccharomyces cerevisiae and binds protein that aids in stabilization of transcripts that contain AU-rich elements or stabilizer elements.
Pub1 is thought to regulate mRNA turnover. Pub1 is majorly found in the cytoplasm but has also been identified in the nucleus.
The hypothesized primary structure of PUB1 shows that it belongs to the family of Ribonucleic acid-binding proteins whose structures are similar to those found in the human hnRNP M proteins.
Gene replacement revealed that PUB1 is not necessary for yeast cells, which implies that protein(s) that do not work with PUB1 is sufficient to sustain viability.
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