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Sequencing of mRNAs with N6-methyladenosine modifications in Diabetic Nephropathy (DN) with and without forced expression of FTO

ABSTRACT: Sequencing of mRNAs with N6-methyladenosine modifications in Diabetic Nephropathy (DN) with and without forced expression of FTO

PROVIDER: PRJNA646696 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12235505_1.fastq.gz	Fastqsanger.gz
	SRR12235505_2.fastq.gz	Fastqsanger.gz
	SRR12235506_1.fastq.gz	Fastqsanger.gz
	SRR12235506_2.fastq.gz	Fastqsanger.gz
	SRR12235507_1.fastq.gz	Fastqsanger.gz

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Sequencing of mRNAs with N6-methyladenosine modifications in Diabetic Nephropathy (DN) with and without forced expression of FTO

Project description:To identify potential mRNA targets of FTO whose m6A levels are affected by FTO in Diabetic Nephropathy (DN), we conducted m6A-seq for messenger RNAs isolated from HMC cells with and without forced expression of FTO.

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Comparison of Blood Transcriptomic Profiles of Healthy, T2D and Diabetic Nephropathy (DN) Reveals FTO as a potential target for DN

Project description:To identify the potential regulators in the progression of diabetic nephropathy (DN), we performed RNA sequencing of blood samples from healthy volunteers, patients with T2D, and patients with DN. Further analyses revealed that FTO was significantly downregulated in blood samples of T2D and DN patients, while the expression of other erasers, writers or readers remained unchanged between disease and healthy groups . Our study thus provides potential molecular mechanisms for DN progression and association of differential gene expression with the functional and structural changes observed in patients with DN.

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Comparison of Blood Transcriptomic Profiles of Healthy, T2D and Diabetic Nephropathy (DN) Reveals FTO as a potential target for DN

Project description:Comparison of Blood Transcriptomic Profiles of Healthy, T2D and Diabetic Nephropathy (DN) Reveals FTO as a potential target for DN

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FTO regulates adult neurogenesis through modulating the dynamics of N6-methyladenosine

Project description:Fat mass and obesity-associated gene (FTO) is a member of the Fe (II) and oxoglutarate-dependent AlkB oxygenase family, and has been linked to obesity and intellectual disability. However, the role of FTO in neurodevelopment and neurogenesis remains largely unknown. Here, we show that FTO is expressed in adult neural stem cells (aNSCs) and neurons, and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to the decreased brain size and body weight. We found that FTO deficiency could reduce the proliferation and neuronal differentiation of aNSCs in vivo, which leads to the impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we further performed the genome-wide m6A profiling and observed the dynamic m6A modification during postnatal neurodevelopment. The loss of FTO could lead to the altered m6A modifications on the mRNAs of several key components of BDNF pathway. These results together suggest that FTO play important roles in neurogenesis and learning and memory.

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Project description:The fat mass and obesity-associated (FTO) protein is a well-characterized demethylase that removes N6-methyladenosine (m6A) from animal mRNAs. However, it is unclear yet how the demethylation operates in living cells. In this study, we applied genome-wide approaches to study how FTO finds its demethylation targets in human cells. We overexpressed FTO in human HeLa cells, demonstrating that FTO effectively removes m6A from the RRACH motif enriched in the 3’UTR regions and leaves m6A at other motifs unaffected. RRACH elements are clearly enriched at FTO binding sites; however, m6A has a lower tendency to be removed from the FTO-bound RRACH. Taken together with the experimental validaton results, we propose a model in which FTO effectivly recognizes m6A-containing RRACH motifs in RNAs, leading to a faster demethylation and dissociation kinetic than the association, and consequently undectable FTO-mRNA association. However, when FTO binds to the non-m6A RRACH motif, the binding has a lower dissociation kinetics, yielding the detectable FTO binding signals which would enable FTO to have roles in regulating other mRNA processing events.

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Project description:Discriminating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) can help provide more specific treatments. However, there are no ideal biomarkers for their differentiation. Thus, the aim of this study was to identify biomarkers for diagnosing and predicting the progression of DN by investigating different salivary glycopatterns. LC-MS/MS were used to screen different glycopatterns in patients with DN or NDRD. Bioinformatics analyses were used to identify corresponding glycoproteins and predict their function

2022-05-19 | PXD030108 | Pride

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