Selectivity of mRNA degradation by autophagy in yeast

Makino, Shiho; Kawamata, Tomoko; Iwasaki, Shigeo; Ohsumi, Yoshinori

doi:10.1038/s41467-021-22574-6

Cited by 39 publications

(42 citation statements)

References 72 publications

(76 reference statements)

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“…Our results demonstrated that NMD factors were expressed at low levels during the EMT and that this expression was inversely correlated with the levels of GABARAPL1 in lung cancer models, suggesting that GABARAPL1 could also be regulated during the EMT at the post-transcriptional level by the NMD pathway as an interplay between mRNA degradation pathway and autophagy. Moreover, crosstalk between autophagy and selective mRNA degradation was previously described in yeast by Makino and collaborators [30], demonstrating that autophagy could selectively target and degrade mRNAs.…”

Section: Discussionmentioning

confidence: 70%

The NMD Pathway Regulates GABARAPL1 mRNA during the EMT

et al. 2021

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EMT is a reversible cellular process that is linked to gene expression reprogramming, which allows for epithelial cells to undergo a phenotypic switch to acquire mesenchymal properties. EMT is associated with cancer progression and cancer therapeutic resistance and it is known that, during the EMT, many stress response pathways, such as autophagy and NMD, are dysregulated. Therefore, our goal was to study the regulation of ATG8 family members (GABARAP, GABARAPL1, LC3B) by the NMD and to identify molecular links between these two cellular processes that are involved in tumor development and metastasis formation. IHC experiments, which were conducted in a cohort of patients presenting lung adenocarcinomas, showed high GABARAPL1 and low UPF1 levels in EMT+ tumors. We observed increased levels of GABARAPL1 correlated with decreased levels of NMD factors in A549 cells in vitro. We then confirmed that GABARAPL1 mRNA was indeed targeted by the NMD in a 3′UTR-dependent manner and we identified four overlapping binding sites for UPF1 and eIF4A3 that are potentially involved in the recognition of this transcript by the NMD pathway. Our study suggests that 3′UTR-dependent NMD might be an important mechanism that is involved in the induction of autophagy and could represent a promising target in the development of new anti-cancer therapies.

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Section: Discussionmentioning

confidence: 70%

The NMD Pathway Regulates GABARAPL1 mRNA during the EMT

et al. 2021

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“…To date, the question of whether that autophagy-induced RNA degradation occurs preferentially or non-selectively is yet to be fully understood [57]. While it was previously suggested that ribosomes are selectively degraded via ribophagy in a Ubp3 (deubiquitinase) -Bre5 (its co-factor) dependent manner [58], findings from Huang and colleagues reported here [49], have shown only temporal delay in RNA degradation for individual Bre5∆ and Ubp3∆ strains relative to wild-type cells.…”

Section: Nitrogen Starvationmentioning

confidence: 87%

“…Further study on Ubp3 demonstrated its mediation on selective degradation of translation and RNA turnover factors under nitrogen-starved conditions [60]. A most recent study has reported that a subset of mRNAs that encodes for amino acid biosynthesis and ribosomal proteins were preferentially delivered to the vacuole by in rapamycininduced autophagy in yeast for subsequent Rny-1 mediated degradation in the vacuole [57].…”

Section: Nitrogen Starvationmentioning

confidence: 99%

Application of Metabolomics in the Study of Starvation-Induced Autophagy in Saccharomyces cerevisiae: A Scoping Review

Nasaruddin

Arifin

2021

JoF

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This scoping review is aimed at the application of the metabolomics platform to dissect key metabolites and their intermediates to observe the regulatory mechanisms of starvation-induced autophagy in Saccharomyces cerevisiae. Four research papers were shortlisted in this review following the inclusion and exclusion criteria. We observed a commonly shared pathway undertaken by S. cerevisiae under nutritional stress. Targeted and untargeted metabolomics was applied in either of these studies using varying platforms resulting in the annotation of several different observable metabolites. We saw a commonly shared pathway undertaken by S. cerevisiae under nutritional stress. Following nitrogen starvation, the concentration of cellular nucleosides was altered as a result of autophagic RNA degradation. Additionally, it is also found that autophagy replenishes amino acid pools to sustain macromolecule synthesis. Furthermore, in glucose starvation, nucleosides were broken down into carbonaceous metabolites that are being funneled into the non-oxidative pentose phosphate pathway. The ribose salvage allows for the survival of starved yeast. Moreover, acute glucose starvation showed autophagy to be involved in maintaining ATP/energy levels. We highlighted the practicality of metabolomics as a tool to better understand the underlying mechanisms involved to maintain homeostasis by recycling degradative products to ensure the survival of S. cerevisiae under starvation. The application of metabolomics has extended the scope of autophagy and provided newer intervention targets against cancer as well as neurodegenerative diseases in which autophagy is implicated.

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“…Autophagy was found to be a self-eating cellular process to maintain cellular homeostasis via lysosome-mediated degradation in yeast [45][46][47] and reviewed regarding various aspects in immunity [48]. It is also a cell intrinsic recycling system of cytoplasmic components and organelles as a defense mechanism that removes pathogens including virus or bacteria and damaged endocytic compartments from the cytosol [49].…”

Section: Autophagymentioning

confidence: 99%

Autoimmune Epithelitis and Chronic Inflammation in Sjögren’s Syndrome-Related Dry Eye Disease

Ogawa

Takeuchi

Tsubota

2021

IJMS

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Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren’s syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.

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Selectivity of mRNA degradation by autophagy in yeast

Cited by 39 publications

References 72 publications

The NMD Pathway Regulates GABARAPL1 mRNA during the EMT

The NMD Pathway Regulates GABARAPL1 mRNA during the EMT

Application of Metabolomics in the Study of Starvation-Induced Autophagy in Saccharomyces cerevisiae: A Scoping Review

Autoimmune Epithelitis and Chronic Inflammation in Sjögren’s Syndrome-Related Dry Eye Disease

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