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PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells

ABSTRACT: PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells

PROVIDER: PRJNA1057278 | ENA |

REPOSITORIES: ENA

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PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells [acRIPseq]

Project description:Massive numbers of modified bases in mRNAs sculpt the epitranscriptome and play vital roles in RNA metabolism. The only known acetylated RNA modification, N-4-acetylcytidine (ac4C), is highly conserved across cell types and among species. Although the GCN5-related acetyltransferase 10 (NAT10) functions as an ac4C writer, the mechanism underlying the acetylation process is largely unknown. In this study, we identified the NAT10/PCBP/TDP43 complex as an mRNA ac4C writer in mammalian cells. We identified RNA-binding proteins (RBPs) affiliated with two different families, PCBP1/2 (poly(rC)-binding protein 1/2) and TDP43 (TAR DNA binding protein 43), as NAT10 adaptors for mRNA tethering and substrate selection. Knockdown of the adaptors resulted in decreased mRNA acetylation abundance in HEK293T cells, with globally reduced density in 5`-untranslated region (UTR) and coding sequence (CDS) and ablated cytidine-rich ac4C motifs. The adaptors also affect the ac4C sites by recruiting NAT10 to their binding sequences. The presence of the NAT10/PCBP/TDP43 complex in mouse testes highlights its potential physiological functions in vivo. These findings reveal the composition of the mRNA ac4C writer complex in mammalian cells and expand our knowledge of mRNA acetylation and ac4C site preferences.

2024-12-27 | GSE252075 | GEO

PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells [293T_acRIPseq]

2024-12-27 | GSE252076 | GEO

PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-12-27 | GSE252077 | GEO

Project description:PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells_293T_acRIP

| PRJNA1006440 | ENA

Project description:PCBP1/2 and TDP43 Function As NAT10 Adaptors In ac4C Writer Complex Towards mRNAs in Mammalian Cells

| PRJNA1005834 | ENA

Transcriptomic ac4C profiling in NAT10 knockdown acute myeloid leukemia cells

Project description:RNA modification represents an important post-transcriptional regulatory mechanism in acute myeloid leukemia (AML), however the function and mechanism of RNA acetylation ac4C in AML remains elusive. Here, we report that NAT10, as the ac4C writing enzyme, plays a critical oncogenic function in AML and represents a promising therapeutic target for AML. To understand the mechanisms underlying the function of NAT10 as an RNA ac4C writer in AML, we profiled ac4C modification in the transcriptome of MOLM13 cells using a refined ac4C RNA immunoprecipitation and high throughput sequencing (RacRIP-seq) protocol, and performed systematic calibration with a modification-free control library generated from the in vitro- transcribed MOLM13 transcriptome (referred to as IVT control) to eliminate most of the false- positive signals. We also applied the RacRIP-seq in NAT10 knockdown and control MOLM13 cells to characterize NAT10 targets.

2024-08-26 | GSE246505 | GEO

chemical ac4C sequencing (ac4C-seq) to identify mRNA ac4C sites

Project description:NAT10-catalyzed N4-acetylcytidine (ac4C) has emerged as a vital post-transcriptional modulator on the coding transcriptome by promoting mRNA stability. To explore the transcriptome-wide profile of ac4C modification, we mapped the locations of ac4C modification on wild-type (WT) hESCs and NAT10 KD hESCs by NaCNBH3-based chemical ac4C sequencing (ac4C-seq).

2023-08-25 | GSE226747 | GEO

chemical ac4C sequencing (ac4C-seq) to identify mRNA ac4C sites

Project description:chemical ac4C sequencing (ac4C-seq) to identify mRNA ac4C sites

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ac4C-RIP-seq to identify mRNA ac4C peaks

2023-08-25 | GSE226748 | GEO

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Project description:The majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the relationship between TDP43’s RNA binding properties and neurodegeneration remain obscure. Here we show that engineered mutations disrupting a salt bridge between TDP43’s RNA recognition motifs interfere with nucleic acid binding and eliminate recognition of native TDP43 substrates. The accumulation of WT TDP43, but not RNA binding-deficient variants, disproportionately affected the abundance and splicing of encoding ribosome and oxidative phosphorylation components.

2019-03-22 | GSE128647 | GEO

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