Plants employ distinct mechanisms to respond to environmental changes. Modification of mRNA by -methyladenosine (mA), known to affect the fate of mRNA, may be one such mechanism to reprogram mRNA processing and translatability upon stress. However, it is difficult to distinguish a direct role from a pleiotropic effect for this modification due to its prevalence in RNA.
View Article and Find Full Text PDFPseudomonas aeruginosa harbors sophisticated transcription factor (TF) networks to coordinately regulate cellular metabolic states for rapidly adapting to changing environments. The extraordinary capacity in fine-tuning the metabolic states enables its success in tolerance to antibiotics and evading host immune defenses. However, the linkage among transcriptional regulation, metabolic states and antibiotic tolerance in P.
View Article and Find Full Text PDFBackground: Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood.
View Article and Find Full Text PDFN6-methyladenosine (m6A) has been increasingly recognized as a new and important regulator of gene expression. To date, transcriptome-wide m6A detection primarily relies on well-established methods using next-generation sequencing (NGS) platform. However, direct RNA sequencing (DRS) using the Oxford Nanopore Technologies (ONT) platform has recently emerged as a promising alternative method to study m6A.
View Article and Find Full Text PDFN-deoxyadenosine methylation (6mA) is the most widespread type of DNA modification in prokaryotes and is also abundantly distributed in some unicellular eukaryotes. However, 6mA levels are remarkably low in mammals. The lack of a precise and comprehensive mapping method has hindered more advanced investigations of 6mA.
View Article and Find Full Text PDFRecent years have witnessed rapid progress in the field of epitranscriptomics. Functional interpretation of the epitranscriptome relies on sequencing technologies that determine the location and stoichiometry of various RNA modifications. However, contradictory results have been reported among studies, bringing the biological impacts of certain RNA modifications into doubt.
View Article and Find Full Text PDFMicrobes employ sophisticated cellular networks encoded by complex genomes to rapidly adapt to changing environments. High-throughput genome engineering methods are valuable tools for functionally profiling genotype-phenotype relationships and understanding the complexity of cellular networks. However, current methods either rely on special homologous recombination systems and are thus applicable in only limited bacterial species or can generate only nonspecific mutations and thus require extensive subsequent screening.
View Article and Find Full Text PDFThe past few years have witnessed rapid progress in the field of RNA modifications. As the most prevailing modification on eukaryotic mRNA, mA is characterized to play a vital role in various cellular activities. However, limitations of the detection method impede functional studies of mA.
View Article and Find Full Text PDFDeficiency of the N -methyladenosine (m A) methyltransferase complex results in global reduction of m A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m A methylation affects cell fate decisions due to the inability to modulate individual m A modification in ESCs with precise temporal control. Here, a targeted RNA m A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs).
View Article and Find Full Text PDFThe RNA modification N-methyladenosine (mA) has critical roles in many biological processes. However, the function of mA in the early phase of mammalian development remains poorly understood. Here we show that the mA reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an mA-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state.
View Article and Find Full Text PDFGenetically identical female honeybee larvae with different diets develop into sterile workers or fertile queens. It remains unknown whether the reversible RNA N-methyladenosine (mA) mark functionally impact this "caste differentiation." Here, we profile the transcriptome-wide mA methylome of honeybee queen and worker larvae at three instar stages and discover that mA methylation dynamics are altered by differential feeding.
View Article and Find Full Text PDFBackground: The adenosine-to-inosine (A-to-I) editing in anticodons of tRNAs is critical for wobble base-pairing during translation. This modification is produced via deamination on A34 and catalyzed by the adenosine deaminase acting on tRNA (ADAT) enzyme. Eukaryotic ADATs are heterodimers composed of the catalytic subunit ADAT2 and the structural subunit ADAT3, but their molecular assemblies and catalytic mechanisms are largely unclear.
View Article and Find Full Text PDFModification on nucleic acid plays a pivotal role in controlling gene expression. Various kinds of modifications greatly increase the information-encoding capacity of DNA and RNA by introducing extra chemical group to existing bases instead of altering the genetic sequences. As a marker on DNA or RNA, nucleic acid modification can be recognized by specific proteins, leading to versatile regulation of gene expression.
View Article and Find Full Text PDF-methyladenosine (mA) is one of the most abundant messenger RNA modifications in eukaryotes involved in various pivotal processes of RNA metabolism. The most popular high-throughput mA identification method depends on the anti-mA antibody but suffers from poor reproducibility and limited resolution. Exact location information is of great value for understanding the dynamics, machinery, and functions of mA.
View Article and Find Full Text PDFBackground: N-methyldeoxyadenosine (6mA or mdA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited.
View Article and Find Full Text PDF-methyladenosine (mA) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by mA-selective 'reader' proteins of the YTH family, which incorporate mA-modified mRNAs into pathways of RNA metabolism. Here, we show that the mA-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells.
View Article and Find Full Text PDFNat Struct Mol Biol
June 2017
The DNA-adenine modification N-methyladenine (6mA), initially thought to be mainly restricted to prokaryotes and certain unicellular eukaryotes, has recently been found in metazoans. Proposed functions vary from gene activation to transposon suppression. However, since most metazoan genomes possess 5-methylcytosine (5mC) as a dominant epigenetic mark, it raises the question of why 6mA is required.
View Article and Find Full Text PDFDNA N-methyldeoxyadenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to exist and play epigenetic roles in eukaryotic DNA. Here we report that 6mA accumulates up to ∼0.1-0.
View Article and Find Full Text PDFHow do different cell types acquire their specific identities and functions is a fundamental question of biology. Previously significant efforts have been devoted to search for cell-type-specifically expressed genes, especially transcription factors, yet how do ubiquitously expressed genes participate in the formation or maintenance of cell-type-specific features remains largely unknown. Here, we have identified 110 mouse embryonic stem cell (mESC) specifically expressed transcripts with cell-stage-specific alternative transcription start sites (SATS isoforms) from 104 ubiquitously expressed genes, majority of which have active epigenetic modification- or stem cell-related functions.
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