Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA

Hao, Wei-Chao; Dian, Mei-Juan; Zhou, Ying; Zhong, QiuLing; Pang, WenQian; Li, Zijian; Zhao, YaYan; Ma, Jiacheng; Lin, Xiaolin; Luo, RenRu; Li, YongLong; Jia, JunShuang; Shen, HongFen; Huang, Shixian; Dai, GuanQi; Wang, Jiahong; Sun, Yan; Xiao, Dong

doi:10.1038/s41467-022-32963-0

Cited by 48 publications

(34 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In carcinogenesis studies, eIF3a has been recognized as a proto-oncogene, and may be a potential anticancer drug target in the eIF family ( 24 ). Recently, researchers found that eIF3a could involve in fibrosis through regulation of the TGF-β1 signaling pathway ( 27 ); the m 6 A reader YTHDF3 could recruit eIF3a to facilitate FOXO3 translation, subsequently initiating autophagy ( 28 ). These findings may provide directions for subsequent studies of eIF3a in the mechanisms of iNOA.…”

Section: Discussionmentioning

confidence: 99%

Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients

Tang

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundGrowing evidence has indicated that epigenetic factors might be associated with the pathophysiology of idiopathic nonobstructive azoospermia (iNOA). As the most common RNA modification, N6-methyladenosine (m6A) methylation has recently attracted more attention in the regulation of spermatogenesis; however, its role in the mechanisms of iNOA is still unclear.ObjectiveTo determine the differential expression of mRNA and m6A methylation status in the testes of iNOA patients.MethodsTestes tissues from diagnosed iNOA and controlled obstructive azoospermia (OA) patients were collected and grouped according to the histological examinations. Total RNA was isolated and quantified by an m6A RNA Methylation Quantification Kit. The expression level of mRNAs was detected by qRT-PCR analysis. Differentially expressed m6A genes were analyzed using the human ArrayStar m6A epitranscriptomic microarray, and bioinformatics analyses were applied.ResultsA total of 36 iNOA and 8 controlled patients were included. The global expression of m6A in the iNOA group was significantly decreased. A dosage relationship was observed between the m6A decline and the degree of impaired spermatogenesis, with the successive process of normal spermatogeneis, hypospermatogenesis (HP), maturation arrest (MA), and Sertoli cell-only syndrome (SO). Four down-expressed genes (BDNF, TMEM38B, RPL3L, and C22orf42) displayed significantly lower expression of m6A methylation. Additionally, they also showed a gradually down-expressed tendency in the three groups (OA, HP, SO/MA groups). Moreover, m6A reader EIF3A was approved to have differential expression through microarrays analysis, which was consistent with the result from the qRT-PCR test.ConclusionsThe m6A expression was gradually downregulated in the testes tissue from iNOA patients in accordance with the degree of spermatogenic dysfunction. The determined differential expression of mRNA and m6A methylation status may represent potentially novel molecular targets for the mechanism study of iNOA in the epigenetic level, which could benefit the understanding of the pathophysiology of iNOA.

show abstract

Section: Discussionmentioning

confidence: 99%

Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients

Tang

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Elevated m6A modifications induced by METTL3 enable YTHDF3 to promote autophagosome formation and lysosomal function upon nutrient deficiency [ 153 ]. YTHDF3 binding to the m6A modifications at the coding DNA sequence (CDS) and 3′ UTR around the stop codon of Foxo3 mRNA facilitated FOXO3 translation and induced autophagy [ 155 ]. Enterovirus-71 (EV-71) infection induced autophagy [ 156 ].…”

Section: The Regulatory Roles Of M6a Writers In Autophagymentioning

confidence: 99%

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

Shim

Jeoung

2023

IJMS

View full text Add to dashboard Cite

RNA methylations play critical roles in RNA processes, including RNA splicing, nuclear export, nonsense-mediated RNA decay, and translation. Regulators of RNA methylations have been shown to be differentially expressed between tumor tissues/cancer cells and adjacent tissues/normal cells. N6-methyladenosine (m6A) is the most prevalent internal modification of RNAs in eukaryotes. m6A regulators include m6A writers, m6A demethylases, and m6A binding proteins. Since m6A regulators play important roles in regulating the expression of oncogenes and tumor suppressor genes, targeting m6A regulators can be a strategy for developing anticancer drugs. Anticancer drugs targeting m6A regulators are in clinical trials. m6A regulator-targeting drugs could enhance the anticancer effects of current chemotherapy drugs. This review summarizes the roles of m6A regulators in cancer initiation and progression, autophagy, and anticancer drug resistance. The review also discusses the relationship between autophagy and anticancer drug resistance, the effect of high levels of m6A on autophagy and the potential values of m6A regulators as diagnostic markers and anticancer therapeutic targets.

show abstract

“…Their results showed that YTHDF3 promotes autophagy by recognizing the modification of m 6 A sites near the stop codon of FOXO3 mRNA. YTHDF3 also recruits eIF3a and eIF4B to facilitate FOXO3 translation, which subsequently initiates autophagy [81]. Liang et al [82] reported that the decrease in m 6 A reader YTHDC1 inhibited autophagy by accelerating sequestosome1 (SQSTM1) nuclear mRNA decay in the keratinocytes of diabetic skin, resulting in impaired migration of keratinocytes and delayed wound healing.…”

Section: Ythdf and Ythdc Familymentioning

confidence: 99%

Novel Insights into The Roles of N⁶-methyladenosine (m⁶A) Modification and Autophagy in Human Diseases

et al. 2023

View full text Add to dashboard Cite

Autophagy is an evolutionarily conserved cellular degradation and recycling process. It is important for maintaining vital cellular function and metabolism. Abnormal autophagy activity can cause the development of various diseases. N 6 -methyladenosine (m 6 A) methylation is the most prevalent and abundant internal modification in eukaryotes, affecting almost all aspects of RNA metabolism. The process of m 6 A modification is dynamic and adjustable. Its regulation depends on the regulation of m 6 A methyltransferases, m 6 A demethylases, and m 6 A binding proteins. m 6 A methylation and autophagy are two crucial and independent cellular events. Recent studies have shown that m 6 A modification mediates the transcriptional and post-transcriptional regulation of autophagy-related genes, affecting autophagy regulatory networks in multiple diseases. However, the regulatory effects of m 6 A regulators on autophagy in human diseases are not adequately acknowledged. In the present review, we summarized the latest knowledge of m 6 A modification in autophagy and elucidated the molecular regulatory mechanisms underlying m 6 A modification in autophagy regulatory networks. Moreover, we discuss the potentiality of m 6 A regulators serving as promising predictive biomarkers for human disease diagnosis and targets for therapy. This review will increase our understanding of the relationship between m 6 A methylation and autophagy, and provide novel insights to specifically target m 6 A modification in autophagy-associated therapeutic strategies.

show abstract

Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA

Cited by 48 publications

References 109 publications

Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients

Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

Novel Insights into The Roles of N⁶-methyladenosine (m⁶A) Modification and Autophagy in Human Diseases

Contact Info

Product

Resources

About

Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA

Cited by 48 publications

References 109 publications

Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients

Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

Novel Insights into The Roles of N6-methyladenosine (m6A) Modification and Autophagy in Human Diseases

Contact Info

Product

Resources

About

Novel Insights into The Roles of N⁶-methyladenosine (m⁶A) Modification and Autophagy in Human Diseases