FTO: An Emerging Molecular Player in Neuropsychiatric Diseases

Annapoorna, P K; Iyer, Harish; Parnaik, Tanvi; Narasimhan, Harish; Bhattacharya, Arnav; Kumar, Arvind

doi:10.1016/j.neuroscience.2019.08.021

Cited by 27 publications

(19 citation statements)

References 113 publications

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“…When m 6 A demethylases such as FTO and Alkbh5 were identified, the precise modification sites of m 6 A as well as their biological functions were broadly revealed [89,151,152,159]. the view of the m 6 A epitranscriptomic landscape has become comprehensible, and conclusively shows that m 6 A is mainly distributed in the coding and…”

Section: The Effects Of M 6 a On Mrnamentioning

confidence: 98%

“…The fractions containing CA-m 6 Am-adding enzymatic activity were isolated from HEK293 cell extracts following the same workflow devised four decades earlier [74,163]. Next, mass spectrometry was used to identify candidate proteins that co-fractionated with the CAm 6 Am-adding activity [159]. Among the proteins in their list, they focused on PCIF1 since its evolutionary conservation suggested that it possessed methyltransferase activity [163,167].…”

Section: Pcif1 the Writer Of Cap-adjacent M 6 Ammentioning

confidence: 99%

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From m6A to Cap-Adjacent m6Am and Their Effects on mRNAs

Tat¹,

Kiss²

2020

Preprint

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Although RNA modifications were discovered decades ago, the identification of enzymes that write, read, and erase RNA modifications enabled their functional study and spawned the field of epitranscriptomics. Coupling that knowledge to new methods has enabled the precise pinpointing of epitranscriptomic modifications across the transcriptome plus the elucidation of their functional consequences. PCIF1 (Phosphorylated CTD Interacting Factor 1) was shown to add N6, 2’-O-dimethyladenosine (m6Am) marks at the first nucleotide after the 5’ N7-methylguanosine (m7G) cap. In this review, we discuss the epitranscriptomic regulation of mRNA in general, and focus on m7G cap-adjacent m6Am in particular. m6Am positions can now be distinguished from N6-methyladenosine (m6A) using new techniques leveraging PCIF1-knockout cells. Although m6Am modification sites can be detected precisely, conflicting data have been published regarding how cap-adjacent m6Am marks affect their host mRNA. Discrepancies in the data mean that the effects of cap-adjacent m6Am on mRNA stability, decapping, and translation continue to be debated. Finally, while PCIF1 is predominantly nuclear, a subset of results suggest a possible cytoplasmic role as well. Taken together, these contradictory results which employed different methodologies and cell lines means that further experiments are required to determine the ultimate biological function(s) of m7G cap-adjacent m6Am.

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Section: The Effects Of M 6 a On Mrnamentioning

confidence: 98%

Section: Pcif1 the Writer Of Cap-adjacent M 6 Ammentioning

confidence: 99%

From m6A to Cap-Adjacent m6Am and Their Effects on mRNAs

Tat¹,

Kiss²

2020

Preprint

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“…37 Therefore, it is not surprising that FTO has been indicated to be involved in neuropsychiatric diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, anxiety and depression. 13 Abnormal expression of FTO demethylase promote tumorigenesis, progression and chemoresistance in several cancers. 14,[38][39][40][41][42][43][44] Significantly high expression of FTO has been observed in cancers compared with adjacent tissues.…”

Section: Biology Of the Fto Demethylase And Its Association With Cancermentioning

confidence: 99%

“…Dysregulation of FTO demethylation has been identified as a driving factor in various diseases, including cancers, metabolic diseases, and neuropsychiatric disorders. [12][13][14] Therefore, efforts have been made to develop small-molecule inhibitors of FTO to probe m 6 A biology and therapeutically target m 6 A modifications, which has been partially reviewed previously. [15][16][17][18] Our review will focus on potential strategies for achieving selective inhibition of FTO over other AlkB homologues, summarize screening methods, and underline the mode of action and potency of FTO inhibitors discovered to date in detail.…”

mentioning

confidence: 99%

Targeting the RNA demethylase FTO for cancer therapy

Zhou

Huang

et al. 2021

RSC Chem. Biol.

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“…Recent studies show that m 6 A and its RMPs, specifically METTL3, YTHDF1 and FTO, play an important role in regulation of stress responses, formation of hippocampal memories, and development of neuropsychiatric diseases [275][276][277]. Furthermore, the FTO-induced hypo-m 6 A levels have been shown to activate the TSC1-mTOR-Tau signaling pathway and increased apoptosis of dopaminergic neurons, which contributes to the pathogenesis of Alzheimer's disease (AD) and Parkinson's disease (PD), respectively [278][279][280].…”

Section: Rna Epigenetics In Neural Disordersmentioning

confidence: 99%

RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases

Willbanks

Wood

Cheng

2021

Genes

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Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases.

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FTO: An Emerging Molecular Player in Neuropsychiatric Diseases

Cited by 27 publications

References 113 publications

From m<sup>6</sup>A to Cap-Adjacent m<sup>6</sup>Am and Their Effects on mRNAs

From m<sup>6</sup>A to Cap-Adjacent m<sup>6</sup>Am and Their Effects on mRNAs

Targeting the RNA demethylase FTO for cancer therapy

RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases

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