A loop matters for FTO substrate selection

Han, Zhifu; Huang, Ning; Niu, Tianhui; Chai, Jijie

doi:10.1007/s13238-010-0082-2

Cited by 5 publications

(5 citation statements)

References 35 publications

(53 reference statements)

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“…Han et al . (22) presented the structural and biochemical work providing insight into the substrate selection mechanisms of FTO , and Rendo et al . (23) reviewed the role of FTO on adiposity based on lifestyle intervention studies in children and adolescents.…”

Section: Research On Fto – Strategies For Novel Obesity‐associated Locimentioning

confidence: 99%

The impact of intronic single nucleotide polymorphisms and ethnic diversity for studies on the obesity gene FTO

2012

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In 2007, the first common genetic variants were identified, which undoubtedly affect our susceptibility to obesity. These variants are located in the fat mass and obesity-associated gene FTO. Since then, over 50 loci for common obesity have been identified. As the research on these loci is still at an early stage, there is a great need to review, for clarification purposes, the current research on FTO, as this is likely to influence future studies. Based on the current knowledge, FTO seems to be directly involved in the regulation of energy intake, but there is an urgent need for the identification of regulatory polymorphisms. Thus, herein, we discuss current knowledge and highlight putative functional regions in FTO based on published data and computer-based analysis.

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Section: Research On Fto – Strategies For Novel Obesity‐associated Locimentioning

confidence: 99%

The impact of intronic single nucleotide polymorphisms and ethnic diversity for studies on the obesity gene FTO

2012

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“…FTO encodes a nuclear protein that is orthologous to proteins of the AlkB family of deoxygenases and appears to function as a DNA or RNA demethylase (Han et al, 2010). In mice and rats, manipulations of Fto gene expression have produced changes in body weight, but not in a consistent direction (Stratigopoulos et al, 2008, 2011; Wang et al, 2011; Tung et al, 2010; Church et al, 2010), and humans heterozygous for null alleles of FTO show no consistent effects on body weight (Meyre et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Hypomorphism for RPGRIP1L, a Ciliary Gene Vicinal to the FTO Locus, Causes Increased Adiposity in Mice

et al. 2014

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Summary Common polymorphisms in the first intron of FTO are associated with a increased body weight in adults. Previous studies have suggested that a CUX1 regulatory element within the implicated FTO region controls expression of FTO and the nearby ciliary gene, RPGRIP1L. Given the role of ciliary genes in energy homeostasis, we hypothesized that mice hypomorphic for Rpgrip1l would display increased adiposity. We find that Rpgrip1l+/− mice are hyperphagic, fatter, and display diminished suppression of food intake in response to leptin administration. In the hypothalamus of Rpgrip1l+/− mice, and in human fibroblasts with hypomorphic mutations in RPGRIP1L, the number of AcIII-positive ciliais diminished, accompanied by impaired convening of the leptin receptor to the vicinity of the cilium, and diminished pStat3 in response to leptin. These findings suggest that RPGRIP1L may be partly or exclusively responsible for the obesity susceptibility signal at the FTO locus.

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“…However, a mere buffer solution cannot recapitulate the tremendous compositional complexity of the cellular environment. Furthermore, changes of molecular environment from one subcellular compartment to another could easily alter the enzyme’s behaviour 44 . In cellulo studies on FTO offer a striking illustration of this.…”

Section: Towards Tissue-specific Function?mentioning

confidence: 99%

“…The C-terminal domain of FTO does not contain essential residues for RNA interaction or FTO activity. Noteworthy, comparative studies have shown that FTO’s C-terminal domain is unique compared to the other ALKBH family members [ 44 , 51 . The versatile activity of FTO is likely due to this domain, through its ability to associate with molecular partners.…”

Section: Determinants Of Multi-substrate Specificity Of Ftomentioning

confidence: 99%

The multifaceted functions of the Fat mass and Obesity-associated protein (FTO) in normal and cancer cells

2022

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The last decade has seen mRNA modification emerge as a new layer of gene expression regulation. The Fat mass and obesity-associated protein (FTO) was the first identified eraser of N6-methyladenosine (m6A) adducts, the most widespread modification in eukaryotic messenger RNA. This discovery, of a reversible and dynamic RNA modification, aided by recent technological advances in RNA mass spectrometry and sequencing has led to the birth of the field of epitranscriptomics. FTO crystallized much of the attention of epitranscriptomics researchers and resulted in the publication of numerous, yet contradictory, studies describing the regulatory role of FTO in gene expression and central biological processes. These incongruities may be explained by a wide spectrum of FTO substrates and RNA sequence preferences: FTO binds multiple RNA species (mRNA, snRNA and tRNA) and can demethylate internal m6A in mRNA and snRNA, N6,2′-O-dimethyladenosine (m6Am) adjacent to the mRNA cap, and N1-methyladenosine (m1A) in tRNA. Here, we review current knowledge related to FTO function in healthy and cancer cells. In particular, we emphasize the divergent role(s) attributed to FTO in different tissues and subcellular and molecular contexts.

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A loop matters for FTO substrate selection

Cited by 5 publications

References 35 publications

The impact of intronic single nucleotide polymorphisms and ethnic diversity for studies on the obesity gene FTO

The impact of intronic single nucleotide polymorphisms and ethnic diversity for studies on the obesity gene FTO

Hypomorphism for RPGRIP1L, a Ciliary Gene Vicinal to the FTO Locus, Causes Increased Adiposity in Mice

The multifaceted functions of the Fat mass and Obesity-associated protein (FTO) in normal and cancer cells

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