The landscape of N-methyadenosine (mA) on different RNA isoforms is still incompletely understood. Here, in HEK293T cells, we endogenously label the methylated mA sites on single Oxford Nanopore Technology (ONT) direct RNA sequencing (DRS) reads by APOBEC1-YTH-induced C-to-U mutations 10-100 nt away, obtaining 1,020,237 5-mer single-read mA signals. We then trained m6Aiso, a deep residual neural network model that accurately identifies and quantifies mA at single-read resolution.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
October 2024
As the most abundant messenger RNA (mRNA) modification, N6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A sequencing (m6A-seq) and RNA sequencing (RNA-seq) samples.
View Article and Find Full Text PDFN6-methyladenosine (mA) is the most abundant endogenous modification in eukaryotic RNAs. It plays important roles in various biological processes and diseases, including cancers. More and more studies have revealed that the deposition of mA is specifically regulated in a context-dependent manner.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
August 2023
Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
August 2023
Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N-methyladenosine (mA) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific mA methylation.
View Article and Find Full Text PDFHippo-YAP signaling pathway functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. We found that knockout (KO) of Mst1 and Mst2, two key components of the Hippo signaling in mouse embryonic stem cells (ESCs), resulted in a disruption of differentiation into mesendoderm lineage. To further uncover the underlying regulatory mechanisms, we performed a series of ChIP-seq experiments with antibodies against YAP, ESC master transcription factors and some characterized histone modification markers as well as RNA-seq assays using wild type and Mst KO samples at ES and day 4 embryoid body stage respectively.
View Article and Find Full Text PDFNucleic Acids Res
February 2020
N6-methyladenosine (m6A) is a reversible and dynamic RNA modification in eukaryotes. However, how cells establish cell-specific m6A methylomes is still poorly understood. Here, we developed a computational framework to systematically identify cell-specific trans regulators of m6A through integrating gene expressions, binding targets and binding motifs of large number of RNA binding proteins (RBPs) with a co-methylation network constructed using large-scale m6A methylomes across diverse cell states.
View Article and Find Full Text PDFPluripotent stem cells (PSCs) harbor constitutive DNA replication stress during their rapid proliferation and the consequent genome instability hampers their applications in regenerative medicine. It is therefore important to understand the regulatory mechanisms of replication stress response in PSCs. Here, we report that mouse embryonic stem cells (ESCs) are superior to differentiated cells in resolving replication stress.
View Article and Find Full Text PDFPluripotent stem cells (PSCs) hold great promise in cell-based therapy, but the genomic instability seen in culture hampers their full application. A greater understanding of the factors that regulate genomic stability in PSCs could help address this issue. Here we describe the identification of Filia as a specific regulator of genomic stability in mouse embryonic stem cells (ESCs).
View Article and Find Full Text PDFFloped (official name Ooep) is specifically and abundantly expressed in mouse oocytes and embryonic stem cells (ESCs). Depletion of Floped from oocytes leads to early embryonic arrest at the 2-cell stage. Although crucial in cleavage stage development, its roles in early embryos as well as in ESCs remain completely unknown.
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