Dataset Information

The biology of FTO: from nucleic acid demethylase to amino acid sensor.

ABSTRACT: Genome-wide association studies have revealed that single-nucleotide polymorphisms in the first intron of the gene encoding fat mass and obesity-associated protein (FTO) are robustly associated with BMI and obesity. Subsequently, this association with body weight, which is replicable across multiple populations and different age groups, has been unequivocally linked to increased food intake. Although evidence from a number of animal models with perturbed FTO expression indicates a role for FTO in energy homeostasis, to date, no conclusive link has been made between the risk alleles and FTO expression or its physiological role. FTO is a nucleic acid demethylase, and a deficiency in FTO leads to a complex phenotype highlighted by postnatal growth retardation, pointing to some fundamental developmental role. Recent emerging data now points to a role for FTO in the sensing of nutrients and the regulation of translation and growth. In this review, we explore the in vivo and in vitro evidence detailing the complex biology of FTO and discuss how these might link to the regulation of body weight.

SUBMITTER: Gulati P

PROVIDER: S-EPMC3764322 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The biology of FTO: from nucleic acid demethylase to amino acid sensor.

Gulati Pawan P Yeo Giles S H GS

Diabetologia 20130730 10

Genome-wide association studies have revealed that single-nucleotide polymorphisms in the first intron of the gene encoding fat mass and obesity-associated protein (FTO) are robustly associated with BMI and obesity. Subsequently, this association with body weight, which is replicable across multiple populations and different age groups, has been unequivocally linked to increased food intake. Although evidence from a number of animal models with perturbed FTO expression indicates a role for FTO i ...[more]

PMID: 23896822

Similar Datasets

Project description:Biochemical strategies that use a combination of synthetic oligonucleotides, thermostable DNA polymerases, and DNA ligases can produce large DNA constructs up to 1 megabase in length. Although these ambitious targets are feasible biochemically, comparable technologies for the chemical synthesis of long DNA strands lag far behind. The best available chemical approach is the solid-phase phosphoramidite method, which can be used to assemble DNA strands up to 150 bases in length. Beyond this point, deficiencies in the chemistry make it impossible to produce pure DNA. A possible alternative approach to the chemical synthesis of large DNA strands is to join together carefully purified synthetic oligonucleotides by chemical methods. Click ligation by the copper-catalyzed azide-alkyne (CuAAC) reaction could facilitate this process. In this Account, we describe the synthesis, characterization, and applications of oligonucleotides prepared by click ligation. The alkyne and azide oligonucleotide strands can be prepared by standard protocols, and the ligation reaction is compatible with a wide range of chemical modifications to DNA and RNA. We have employed click ligation to synthesize DNA constructs up to 300 bases in length and much longer sequences are feasible. When the resulting triazole linkage is placed in a PCR template, various DNA polymerases correctly copy the entire base sequence. We have also successfully demonstrated both in vitro transcription and rolling circle amplification through the modified linkage. This linkage has shown in vivo biocompatibility: an antibiotic resistance gene containing triazole linkages functions in E. coli . Using click ligation, we have synthesized hairpin ribozymes up to 100 nucleotides in length and a hammerhead ribozyme with the triazole linkage located at the substrate cleavage site. At the opposite end of the length scale, click-ligated, cyclic mini-DNA duplexes have been used as models to study base pairing. Cyclic duplexes have potential therapeutic applications. They have extremely high thermodynamic stability, have increased resistance to enzymatic degradation, and have been investigated as decoys for regulatory proteins. For potential nanotechnology applications, we have synthesized double stranded DNA catenanes by click ligation. Other researchers have studied covalently fixed multistranded DNA constructs including triplexes and quadruplexes.

Dataset Information

The biology of FTO: from nucleic acid demethylase to amino acid sensor.

Publications

The biology of FTO: from nucleic acid demethylase to amino acid sensor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets