scholarly journals Dynamic m6A methylation facilitates mRNA triaging to stress granules

2018 ◽  
Author(s):  
Maximilian Anders ◽  
Irina Chelysheva ◽  
Ingrid Goebel ◽  
Timo Trenkner ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Messenger Rna ◽  
Stress Granules ◽  
Rna Metabolism ◽  
Methylation Pattern ◽  
Domain Family ◽  
Induced Stress ◽  
And Function ◽  
Selective Mechanism

Summary blurbm6A-modification in the 5’ vicinity of the coding sequence of transcripts provides a selective mechanism for triaging mRNAs to stress granules and is mediated by YTHDF3 ‘reader’ protein.AbstractReversible post-transcriptional modifications on messenger RNA emerge as prevalent phenomena in RNA metabolism. The most abundant among them is N6-methyladenosine (m6A) which is pivotal for RNA metabolism and function, its role in stress response remains elusive. We have discovered that in response to oxidative stress, transcripts are additionally m6A-modified in their 5’ vicinity. Distinct from that of the translationally-active mRNAs, this methylation pattern provides a selective mechanism for triaging mRNAs from the translatable pool to stress-induced stress granules. These stress-induced newly methylated sites are selectively recognized by the YTH domain family 3 (YTHDF3) ‘reader’ protein, thereby revealing a new role for YTHDF3 in shaping the selectivity of stress response. Our findings describe a previously unappreciated function for RNA m6A modification in the oxidative-stress response and expand the breadth of physiological roles of m6A.

scholarly journals Dynamic m6A methylation facilitates mRNA triaging to stress granules

2018 ◽  
Vol 1 (4) ◽  
pp. e201800113 ◽  
Author(s):  
Maximilian Anders ◽  
Irina Chelysheva ◽  
Ingrid Goebel ◽  
Timo Trenkner ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Messenger Rna ◽  
Stress Granules ◽  
Rna Metabolism ◽  
Methylation Pattern ◽  
Domain Family ◽  
Induced Stress ◽  
And Function ◽  
Selective Mechanism

Reversible post-transcriptional modifications on messenger RNA emerge as prevalent phenomena in RNA metabolism. The most abundant among them is N6-methyladenosine (m6A) which is pivotal for RNA metabolism and function; its role in stress response remains elusive. We have discovered that in response to oxidative stress, transcripts are additionally m6A modified in their 5′ vicinity. Distinct from that of the translationally active mRNAs, this methylation pattern provides a selective mechanism for triaging mRNAs from the translatable pool to stress-induced stress granules. These stress-induced newly methylated sites are selectively recognized by the YTH domain family 3 (YTHDF3) “reader” protein, thereby revealing a new role for YTHDF3 in shaping the selectivity of stress response. Our findings describe a previously unappreciated function for RNA m6A modification in oxidative-stress response and expand the breadth of physiological roles of m6A.

scholarly journals DHA-induced stress response in human colon cancer cells – Focus on oxidative stress and autophagy

2016 ◽  
Vol 90 ◽  
pp. 158-172 ◽  
Author(s):  
Kristine Pettersen ◽  
Vivi Talstad Monsen ◽  
Caroline Hild Hakvåg Pettersen ◽  
Hilde Bremseth Overland ◽  
Grete Pettersen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colon Cancer ◽  
Stress Response ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Induced Stress ◽  
Human Colon Cancer Cells

scholarly journals Relevance of oxidative stress in inhibition of eIF2 alpha phosphorylation and stress granules formation during Usutu virus infection

2021 ◽  
Vol 15 (1) ◽  
pp. e0009072
Author(s):  
Ana-Belén Blázquez ◽  
Miguel A. Martín-Acebes ◽  
Teresa Poderoso ◽  
Juan-Carlos Saiz
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Stress Responses ◽  
Stress Granules ◽  
Initiation Factor ◽  
Potential Health ◽  
Usutu Virus ◽  
Cellular Environment ◽  
Infected Cells

Usutu virus (USUV) is an African mosquito-borne flavivirus closely related to West Nile, Japanese encephalitis, Zika, and dengue viruses. USUV emerged in 1996 in Europe, where quickly spread across the continent causing a considerable number of bird deaths and varied neurological disorders in humans, including encephalitis, meningoencephalitis, or facial paralysis, thus warning about USUV as a potential health threat. USUV replication takes place on the endoplasmic reticulum (ER) of infected cells, inducing ER stress and resulting in the activation of stress-related cellular pathways collectively known as the integrated stress response (ISR). The alpha subunit of the eukaryotic initiation factor eIF2 (eIF2α), the core factor in this pathway, is phosphorylated by stress activated kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), heme-regulated inhibitor kinase (HRI), and general control non-repressed 2 kinase (GCN2). Its phosphorylation results, among others, in the downstream inhibition of translation with accumulation of discrete foci in the cytoplasm termed stress granules (SGs). Our results indicated that USUV infection evades cellular stress response impairing eIF2α phosphorylation and SGs assembly induced by treatment with the HRI activator ArsNa. This protective effect was related with oxidative stress responses in USUV-infected cells. Overall, these results provide new insights into the complex connections between the stress response and flavivirus infection in order to maintain an adequate cellular environment for viral replication.

Loading-Induced Stress Response in the Intervertebral Disc

2014 ◽  
Vol 4 (1_suppl) ◽  
pp. s-0034-1376604-s-0034-1376604
Author(s):  
W. H. Chooi ◽  
S. C. Chan ◽  
B. Gantenbein-Ritter ◽  
B. P. Chan
Keyword(s):  
Stress Response ◽  
Intervertebral Disc ◽  
Induced Stress
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