A5007262920- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Carcinogens and Genotoxicity Assessment
- Mosquito-borne diseases and control
- Effects and risks of endocrine disrupting chemicals
- Lipid metabolism and disorders
- Genetically Modified Organisms Research
- interferon and immune responses
- Viral Infections and Vectors
University of Pennsylvania
2019-2024
Philadelphia University
2022
University of Leicester
2009
The posttranscriptional modification of messenger RNA (mRNA) and transfer (tRNA) provides an additional layer regulatory complexity during gene expression. Here, we show that a tRNA methyltransferase, TRMT10A, interacts with mRNA demethylase FTO (ALKBH9), both in vitro inside cells. TRMT10A installs N 1 -methylguanosine (m G) tRNA, performs demethylation on 6 -methyladenosine A) ,2′- O -dimethyladenosine A m ) mRNA. We ablation not only leads to decreased G but also significantly increases...
N6 -methyladenosine (m 6 A) is the most abundant modification on messenger RNAs (mRNAs) and catalyzed by methyltransferase-like protein 3 (Mettl3). To understand role of m A in a self-renewing somatic tissue, we deleted Mettl3 epidermal progenitors vivo. Mice lacking demonstrate marked features dysfunctional development self-renewal, including loss hair follicle morphogenesis impaired cell adhesion polarity associated with oral ulcerations. We show that promotes A-mediated degradation mRNAs...
The Comet assay (CA) is a sensitive/simple measure of genotoxicity. However, many features CA contribute variability. To minimize these, we have introduced internal standard materials consisting 'reference' cells which their DNA substituted with BrdU. Using fluorescent anti -BrdU antibody, plus an additional barrier filter, comets derived from these could be readily distinguished the 'test'-cell comets, present in same gel. In experiments to evaluate reference cell as external and standards,...
rRNA-modifying enzymes participate in ribosome assembly. However, whether the catalytic activities of these are important for assembly and other cellular processes is not fully understood. Here, we report crystal structure WT human dimethyladenosine transferase 1 (DIMT1), an 18
Dimethyladenosine transferase 1 (DIMT1) is an evolutionarily conserved RNA N
Several rRNA-modifying enzymes install rRNA modifications while participating in ribosome assembly. Here, we show that 18 S methyltransferase DIMT1 is essential for acute myeloid leukemia (AML) proliferation through a noncatalytic function. We reveal targeting positively charged cleft of DIMT1, remote from the catalytic site, weakens binding to and mislocalizes nucleoplasm, contrast primarily nucleolar localization wild-type DIMT1. Mechanistically, required undergo liquid–liquid phase...
The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) measure nascent fasting refeeding as well define specific role in mediating this response. We identified 599 feeding-regulated transcripts, over 6,000 eRNAs, mapped their dependency on signaling. Further, several lncRNAs, including lncRNA Gm11967, whose expression was dependent upon liver Akt-FoxO1 axis. Restoring...
Abstract Enzyme-mediated modifications of tRNA, such as 5-methylcytosine (m5C) installed by nuclear-enriched NOP2/Sun RNA methyltransferase 2 (NSUN2), play a critical role in neuronal development and function. However, our understanding these modifications' spatial installation biological functions remains incomplete. In this study, we demonstrate that nucleoplasm-localized G679R NSUN2 mutant, linked to intellectual disability, diminishes NSUN2-mediated tRNA m5C human cell lines Drosophila....
The balance between epithelial stemness and differentiation requires the precise regulation of gene expression programs. Epitranscriptomic RNA modifications have been implicated in both development as well cancers. However, underlying mechanisms are poorly understood. Here, we show that deletion m 6 A methyltransferase, METTL3, impairs A-mediated degradation numerous mRNA transcripts encoding critical chromatin modifying enzymes, resulting widespread abnormalities aberrant cutaneous oral...
Abstract Several rRNA modifying enzymes install modifications while participating in ribosome assembly. Here, we show that 18 S methyltransferase DIMT1 is essential for acute myeloid leukemia (AML) proliferation through a non-catalytic function. We reveal targeting positively charged cleft of DIMT1, remote from the catalytic site, weakens binding to and mis-localizes nucleoplasm, contrast with primarily nucleolar localization wild-type DIMT1. Mechanistically, required undergo liquid-liquid...