Project description:The goal of this study is to investigate how NAT10 regulates heart development in mice. mRNA profiles in hearts of Nat10flox/flox and cardiomyocyte-specific Nat10 knockout (Nat10-CKO) mice at 10 days old were generated by deep sequencing using Illumina novaseq x plus (n=3 for each group).
Project description:The goal of this study is to investigate whether RNA binding activity and acetyltransferase enzyme activity of NAT10 regulates heart development
Project description:The goal of this project is to investigate the role of SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, in the regulation of heart development. SIRT1 is important for heart development and functions. However, the underlying molecular mechanisms remain undefined. In this study, we analyzed the gene expression profiles in E18.5 WT and SIRT1 KO mouse hearts.
Project description:Calcific aortic valve disease is characterized by osteogenic differentiation and calcification of human valve interstitial cells. We found that NAT10 expression was increased in calcified human aortic valves and that NAT10 positively regulates the calcification of valve interstitial cells. To investigate the downstream regulatory molecules of NAT10 in human valve interstitial cells, RNA-seq was performed in cells with NAT10 knockdown and matched negative controls. Transcriptomic comparison between shNAT10 and shNC groups was used to identify NAT10-regulated genes and pathways potentially involved in valve interstitial cell calcification. These data provide a molecular resource for understanding the role of NAT10 in the regulation of human valve interstitial cell function and calcific aortic valve disease.
Project description:The goal of this study is to identify ribosome-protected mRNA fragments (RPFs) to investigate gene expression dynamics at both transcriptional and translational levels associated with NAT10 in mouse hearts
Project description:During mammalian follicular development, the correct establishment of the epitranscriptome in oocytes is essential for precise gene repression and the acquisition of developmental competence. N4-acetylcytidine (ac4C) is a conserved posttranscriptional RNA modification catalyzed by the only known “writer”, N-acetyltransferase 10 (NAT10). NAT10-targeted transcripts in oocytes and their functions in supporting folliculogenesis are poorly understood. In this study, we showed that oocyte-specific knockout of Nat10 resulted in retardation of oocyte growth with defective follicular development, premature ovarian failure, and female sterility. We profiled the ac4C landscape in the ovarian transcriptome and identified many folliculogenesis-related oocyte genes with ac4C modifications. Loss of Nat10 in oocytes eliminated ac4C signals, resulting in the downregulation of numerous oocyte-derived transcripts with reduced stability. Moreover, Nat10-deletion in oocytes or mutations in these ac4C sites led to decreased levels of protein translation, whereas the introduction of ac4C into these mRNAs increased their translational efficiencies. In addition, our data showed that the distinct gene expression patterns in granulosa cells within arrested secondary follicles were disrupted, and the identity of granulosa cells was altered by Nat10 deletion in oocytes. Taken together, these findings provide evidence that NAT10-mediated ac4C modification is a crucial regulatory factor in the maintenance of oocyte competence and that it constitutes a checkpoint for ovarian folliculogenesis beyond the secondary follicle stage.
