Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis

Li, Liping; Zang, Liqun; Zhang, Feiran; Chen, Junchen; Shen, Hui; Shu, Liqi; Liang, Feng; Feng, Chunyue; Deng, Chen; Tao, Hongbing; Xu, Tianlei; Li, Ziyi; Kang, Yunhee; Wu, Hao; Tang, Lichun; Zhang, Pumin; Jin, Peng; Shu, Qiang; Li, Xuekun

doi:10.1093/hmg/ddx128

Cited by 251 publications

(236 citation statements)

References 53 publications

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“…Interestingly, FTO constitutive knockout mice exhibit an impairment in spatial learning tasks (Li et al . ). This is not surprising given the developmental effect displayed in the FTO knockout mouse.…”

Section: Physiological Importance Of M6a In the Central Nervous Systemmentioning

confidence: 97%

“…Notably, FTO has been shown to be required for neural differentiation (Li et al . ), adipogenesis (Zhao et al . ; Zhang et al .…”

Section: The M6a‐machineriesmentioning

confidence: 99%

“…Similar to m6A writers, FTO is predominantly detected in the nucleus (Jia et al 2011). Manipulations of FTO expression in vivo lead to changes in cellular m6A levels (Jia et al 2011;Hess et al 2013;Widagdo et al 2016;Li et al 2017b). However, in the FTO knockout mouse, the effect on the total m6A level is small and seems to involve only a subset of m6A-target mRNAs (Hess et al 2013).…”

Section: The M6a-machineriesmentioning

confidence: 99%

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The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

Widagdo

Anggono

2018

Journal of Neurochemistry

127

103

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Research over the past decade has provided strong support for the importance of various epigenetic mechanisms, including DNA and histone modifications in regulating activity-dependent gene expression in the mammalian central nervous system. More recently, the emerging field of epitranscriptomics revealed an equally important role of post-transcriptional RNA modifications in shaping the transcriptomic landscape of the brain. This review will focus on the methylation of the adenosine base at the N6 position, termed N methyladenosine (m6A), which is the most abundant internal modification that decorates eukaryotic messenger RNAs. Given its prevalence and dynamic regulation in the adult brain, the m6A-epitranscriptome provides an additional layer of regulation on RNA that can be controlled in a context- and stimulus-dependent manner. Conceptually, m6A serves as a molecular switch that regulates various aspects of RNA function, including splicing, stability, localization, or translational control. The versatility of m6A function is typically determined through interaction or disengagement with specific classes of m6A-interacting proteins. Here we review recent advances in the field and provide insights into the roles of m6A in regulating brain function, from development to synaptic plasticity, learning, and memory. We also discuss how aberrant m6A signaling may contribute to neurodevelopmental and neuropsychiatric disorders.

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Section: Physiological Importance Of M6a In the Central Nervous Systemmentioning

confidence: 97%

“…Notably, FTO has been shown to be required for neural differentiation (Li et al . ), adipogenesis (Zhao et al . ; Zhang et al .…”

Section: The M6a‐machineriesmentioning

confidence: 99%

Section: The M6a-machineriesmentioning

confidence: 99%

See 1 more Smart Citation

The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

Widagdo

Anggono

2018

Journal of Neurochemistry

127

103

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“…Therefore, FTO association to obesity may predispose individuals to T2D. Recent studies indicate that FTO may play a role in neurogenesis (Li et al, ) and myogenesis (Wang et al, ), both of which are also affected in diabetes. Further studies are needed to characterize the contribution of FTO to diabetic complications including neuropathy, nephropathy, and myopathy (Table ).…”

Section: Rbps Implicated In Diabetesmentioning

confidence: 99%

Emerging roles of RNA‐binding proteins in diabetes and their therapeutic potential in diabetic complications

Nutter

Kuyumcu‐Martinez

2017

WIREs RNA

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Diabetes is a debilitating health care problem affecting 422 million people around the world. Diabetic patients suffer from multisystemic complications that can cause mortality and morbidity. Recent advancements in high-throughput next-generation RNA-sequencing and computational algorithms led to the discovery of aberrant posttranscriptional gene regulatory programs in diabetes. However, very little is known about how these regulatory programs are mis-regulated in diabetes. RNA-binding proteins (RBPs) are important regulators of posttranscriptional RNA networks, which are also dysregulated in diabetes. Human genetic studies provide new evidence that polymorphisms and mutations in RBPs are linked to diabetes. Therefore, we will discuss the emerging roles of RBPs in abnormal posttranscriptional gene expression in diabetes. Questions that will be addressed are: Which posttranscriptional mechanisms are disrupted in diabetes? Which RBPs are responsible for such changes under diabetic conditions? How are RBPs altered in diabetes? How does dysregulation of RBPs contribute to diabetes? Can we target RBPs using RNA-based methods to restore gene expression profiles in diabetic patients? Studying the evolving roles of RBPs in diabetes is critical not only for a comprehensive understanding of diabetes pathogenesis but also to design RNA-based therapeutic approaches for diabetic complications. WIREs RNA 2018, 9:e1459. doi: 10.1002/wrna.1459 This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing Translation > Translation Regulation.

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“…N 6 -methyladenosine (m 6 A) is one of the most common modification in mRNA, rRNA, tRNA, microRNA and long noncoding RNA (2,3). More recently, it has been reported that the m 6 A methylation plays important roles in the regulation of the circadian clock, meiosis, mRNA degradation and translation as well as microRNA processing (3–7), and moreover, dysregulation of this modification is linked with cancer (8) as well as neurogenesis, learning and memory (9). …”

Section: Introductionmentioning

confidence: 99%

SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

Hou

Zhang

et al. 2018

Nucleic Acids Research

242

176

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The methyltransferase like 3 (METTL3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNAs including mRNA, tRNA, rRNA, small nuclear RNA, microRNA precursor and long non-coding RNA. However, the characteristics of METTL3 in activation and post-translational modification (PTM) is seldom understood. Here we find that METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1. SUMOylation of METTL3 does not alter its stability, localization and interaction with METTL14 and WTAP, but significantly represses its m6A methytransferase activity resulting in the decrease of m6A levels in mRNAs. Consistently with this, the abundance of m6A in mRNAs is increased with re-expression of the mutant METTL3-4KR compared to that of wild-type METTL3 in human non-small cell lung carcinoma (NSCLC) cell line H1299-shMETTL3, in which endogenous METTL3 was knockdown. The alternation of m6A in mRNAs and subsequently change of gene expression profiles, which are mediated by SUMOylation of METTL3, may directly influence the soft-agar colony formation and xenografted tumor growth of H1299 cells. Our results uncover an important mechanism for SUMOylation of METTL3 regulating its m6A RNA methyltransferase activity.

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Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis

Cited by 251 publications

References 53 publications

The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

Emerging roles of RNA‐binding proteins in diabetes and their therapeutic potential in diabetic complications

SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

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