scholarly journals Context-Dependent Roles of RNA Modifications in Stress Responses and Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 1949
Author(s):  
Emma Wilkinson ◽  
Yan-Hong Cui ◽  
Yu-Ying He
Keyword(s):  
Stress Responses ◽  
Cell Biology ◽  
Developmental Disorders ◽  
Metabolic Diseases ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Rna Modifications ◽  
Cellular Stress Responses ◽  
Response To Stress

RNA modifications are diverse post-transcriptional modifications that regulate RNA metabolism and gene expression. RNA modifications, and the writers, erasers, and readers that catalyze these modifications, serve as important signaling machineries in cellular stress responses and disease pathogenesis. In response to stress, RNA modifications are mobilized to activate or inhibit the signaling pathways that combat stresses, including oxidative stress, hypoxia, therapeutic stress, metabolic stress, heat shock, DNA damage, and ER stress. The role of RNA modifications in response to these cellular stressors is context- and cell-type-dependent. Due to their pervasive roles in cell biology, RNA modifications have been implicated in the pathogenesis of different diseases, including cancer, neurologic and developmental disorders and diseases, and metabolic diseases. In this review, we aim to summarize the roles of RNA modifications in molecular and cellular stress responses and diseases.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

2018 ◽  
Vol 475 (6) ◽  
pp. 1037-1057 ◽  
Author(s):  
Alex B. Addinsall ◽  
Craig R. Wright ◽  
Sof Andrikopoulos ◽  
Chris van der Poel ◽  
Nicole Stupka
Keyword(s):  
Metabolic Disease ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Metabolic Dysfunction ◽  
Iodothyronine Deiodinase ◽  
Inflammatory Stress ◽  
Cellular Stress Responses

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.

scholarly journals The Intricate Role of p53 in Adipocyte Differentiation and Function

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2621
Author(s):  
Yun Kyung Lee ◽  
Yu Seong Chung ◽  
Ji Hye Lee ◽  
Jin Mi Chun ◽  
Jun Hong Park
Keyword(s):  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Metabolic Stress ◽  
Health Concern ◽  
Metabolic Dysfunction ◽  
Direct Role ◽  
Proliferation And Apoptosis ◽  
Response To Stress ◽  
And Function

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

scholarly journals Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses

2020 ◽  
Author(s):  
Krzysztof Kolmus ◽  
Purevsuren Erdenebat ◽  
Blair Stewig ◽  
Ewelina Szymańska ◽  
Krzysztof Goryca ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Stress Responses ◽  
Cell Biology ◽  
Cellular Stress ◽  
Mitogen Activated Protein Kinase ◽  
Endosomal Sorting ◽  
Mitogen Activated Protein ◽  
Transcriptional Alterations ◽  
Cellular Stress Responses ◽  
Redundant Functions

ABSTRACTMolecular details of how endocytosis contributes to oncogenesis remain elusive. Our in silico analysis of colorectal cancer (CRC) patients revealed stage-dependent alterations in the expression of 113 endocytosis-related genes. Among them transcription of the Endosomal Sorting Complex Required for Transport (ESCRT)-I component VPS37B was decreased in the advanced stages of CRC. Expression of other ESCRT-I core subunits remained unchanged in the investigated dataset. We analyzed an independent cohort of CRC patients showing also reduced VPS37A mRNA and protein abundance. Transcriptomic profiling of CRC cells revealed non-redundant functions of Vps37 proteins. Knockdown of VPS37A and VPS37B triggered p21-mediated inhibition of cell proliferation and sterile inflammatory response driven by the Nuclear Factor (NF)-κB transcription factor and associated with mitogen-activated protein kinase signaling. Co-silencing of VPS37C further potentiated activation of these independently induced processes. The type and magnitude of transcriptional alterations correlated with the differential ESCRT-I stability upon individual and concurrent Vps37 depletion. Our study provides novel insights into cancer cell biology by describing cellular stress responses that are associated with ESCRT-I destabilization, which might occur in CRC patients.SUMMARY STATEMENTEndosomal Sorting Complex Required for Transport (ESCRT)-I destabilization upon concurrent depletion of Vps37 proteins is linked to the activation of sterile inflammatory response and cell growth inhibition.

The Role of PARP-1 in Host-Pathogen Interaction and Cellular Stress Responses

2015 ◽  
Vol 25 (2) ◽  
pp. 175-190 ◽  
Author(s):  
Hui Li ◽  
Qiming Li ◽  
Wu Li ◽  
Longxiang Xie ◽  
Mingliang Zhou ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cellular Stress ◽  
Host Pathogen Interaction ◽  
Host Pathogen ◽  
Cellular Stress Responses ◽  
Parp 1

scholarly journals Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses

2021 ◽  
Vol 134 (1) ◽  
pp. jcs250951
Author(s):  
Krzysztof Kolmus ◽  
Purevsuren Erdenebat ◽  
Ewelina Szymańska ◽  
Blair Stewig ◽  
Krzysztof Goryca ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cell Biology ◽  
Cellular Stress ◽  
Mitogen Activated Protein Kinase ◽  
Endosomal Sorting ◽  
Mitogen Activated Protein ◽  
Transcriptional Alterations ◽  
Cellular Stress Responses ◽  
Redundant Functions ◽  
Protein Kinase Signaling

ABSTRACTMolecular details of how endocytosis contributes to oncogenesis remain elusive. Our in silico analysis of colorectal cancer (CRC) patients revealed stage-dependent alterations in the expression of 112 endocytosis-related genes. Among them, transcription of the endosomal sorting complex required for transport (ESCRT)-I component VPS37B was decreased in the advanced stages of CRC. Expression of other ESCRT-I core subunits remained unchanged in the investigated dataset. We analyzed an independent cohort of CRC patients, which also showed reduced VPS37A mRNA and protein abundance. Transcriptomic profiling of CRC cells revealed non-redundant functions of Vps37 proteins. Knockdown of VPS37A and VPS37B triggered p21 (CDKN1A)-mediated inhibition of cell proliferation and sterile inflammatory response driven by the nuclear factor (NF)-κB transcription factor and associated with mitogen-activated protein kinase signaling. Co-silencing of VPS37C further potentiated activation of these independently induced processes. The type and magnitude of transcriptional alterations correlated with the differential ESCRT-I stability upon individual and concurrent Vps37 depletion. Our study provides novel insights into cancer cell biology by describing cellular stress responses that are associated with ESCRT-I destabilization.

The effect of zinc and the role of p53 in copper-induced cellular stress responses

2013 ◽  
Vol 33 (7) ◽  
pp. 527-536 ◽  
Author(s):  
Alessia Formigari ◽  
Elisa Gregianin ◽  
Paola Irato
Keyword(s):  
Stress Responses ◽  
Cellular Stress ◽  
Cellular Stress Responses

scholarly journals Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jie Yu ◽  
Peiwei Chai ◽  
Minyue Xie ◽  
Shengfang Ge ◽  
Jing Ruan ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Regulation Of Gene Expression ◽  
Metabolic Stress ◽  
Ocular Melanoma ◽  
Rna Modifications ◽  
M1 Macrophage ◽  
Melanoma Therapy

Abstract Background Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear. Results Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma. Conclusion We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

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