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N6-Methyladenosine

Until now, over 100 types of cellular RNA modifications have been identified in both coding and a variety of non-coding RNAs. N6-methyladenosine (m6A) is the most prevalent and abundant mRNA modification on eukaryote mRNA. The presence of m6A mRNA modifications contributes to diverse fundamental cellular functions, such as pre-mRNA splicing, nuclear transport, stability, translation, and microRNA biogenesis, implying an association with numerous human diseases.

Background of m6A Modification

m6A was discovered in the 1970s in a wide range of cellular mRNAs. m6A modifications are being mapped at the nucleotide level. Methylation occurs at the sixth position of nitrogen atoms of adenosine at the post-transcriptional level with S-adenosylmethionine serving as the methyl donor for m6A formation, which is termed m6A modification. m6A modifications are tied to most aspects of the mRNA life cycle. Under regulatory control by the Mettl3/Mettl14 methyltransferase complex, m6A is the most prevalent internal mRNA modification. m6A depletion by Mettl14 knockout in embryonic mouse brains prolongs the cell cycle of radial glia cells and extends cortical neurogenesis into postnatal stages. m6A depletion by Mettl3 knockdown also leads to a prolonged cell cycle and maintenance of radial glia cells.

Roles of the N6-methyladenosine Writer, Eraser and Reader complexes in regulating mRNA. RNA m6A modifications serve important roles in the molecular mechanisms of gene biology.Fig.1 Roles of the N6-methyladenosine Writer, Eraser and Reader complexes in regulating mRNA. RNA m6A modifications serve important roles in the molecular mechanisms of gene biology. (Zhu, 2019)

Biological Functions of m6A Modifications

The biological functions of RNA m6A modifications occur at three different levels: 1) At the molecular level, RNA modification posttranscriptionally regulates RNA splicing, transport, translation, stability, and localization. 2) At the cellular level, RNA m6A modifications determine the fate of mammalian embryonic stem cells (mESCs). All the findings suggest that m6A modification plays a powerful and precise regulatory role in cell developmental programs. 3) At the physiological level, reversible m6A modification has various consequences. Studies have found that m6A modification is related to neural stem cells, brain development, Parkinson’s disease, and mental illness. Furthermore, m6A modification has been found to have an impact on tumor initiation and progression through various mechanisms.

m6A mRNA Modification Service

The subsequent focus on researching m6A modification in the setting of physiological and pathological processes will enrich our knowledge concerning a variety of conditions, contribute to the advancement of the biological sciences and provide us with novel therapeutic strategies. With Ph.D. level scientists and extensive experience in custom mRNA synthesis and modification, we are dedicated to offering high-quality m6A mRNA modification service to meet our clients’ R&D timeline and budget.

Moreover, we provide a range of methods for the analysis of m6A modifications:

  • Semi-quantitative approaches, including blot technology, methyl sensitivity of MazF RNA endonucleases and immune-northern blot.
  • Quantitative approaches, including RNA photo-crosslinkers and quantification, proteomics, electrochemical immunosensor method, support vector machine-based method.
  • Approaches to detect precise locations, including high-resolution melting analysis (HRM), level and isoform characterization (LAIC), site‑specific cleavage and radioactive labeling followed by ligation-assisted extraction and thin layer chromatography (SCARLET), methylated RNA immunoprecipitation sequencing (MeRIP-seq), m6A individual-nucleotide-resolution cross-linking and immunoprecipitation (MiClip), DNA polymerase for direct m6A sequencing and high-performance liquid chromatography (HPLC).

Highlights

  • State-of-the-art technologies as well as substantial experience and expertise in m6A mRNA modification
  • Diverse strategies for the detection of m6A modifications
  • Top-rated customer experience
  • Reliability and information security
  • Competitive price

m6A modification has become increasingly attractive. Professional technical scientists, comprehensive powerful platform, and abundant experience in m6A mRNA modification make Creative Biolabs a perfect partner to help our clients in the development of related projects. For more detailed information, please feel free to contact us or directly send us an inquiry.

Reference

  1. Zhu, W.; et al. Detection of N6‑methyladenosine modification residues. International journal of molecular medicine. 2019, 43(6):2267-78.
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