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Exploring the epitranscriptome by native RNA sequencing.

Oguzhan Begik1, John S Mattick2, Eva Maria Novoa1,3

  • 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona 08003, Spain.

RNA (New York, N.Y.)
|September 14, 2022
PubMed
Summary
This summary is machine-generated.

Chemical RNA modifications, known as the epitranscriptome, fine-tune gene expression. New sequencing methods like nanopore technology can map these modifications, but a global effort is needed to understand all RNA modification signatures.

Keywords:
RNA modificationsepitranscriptomicsnanopore sequencingnative RNA sequencing

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Chemical RNA modifications, collectively termed the epitranscriptome, are crucial for regulating gene expression.
  • Advancements in high-throughput sequencing have improved the analysis of RNA modifications.
  • Nanopore sequencing enables direct mapping of native RNA modifications, including N6-methyladenosine (m 6 )A, pseudouridine ( Ψ ), and inosine (I).

Purpose of the Study:

  • To highlight the importance of understanding RNA modification signatures.
  • To address the limitations in current knowledge regarding signal modulations by various RNA modifications.
  • To advocate for a comprehensive global effort to characterize the full spectrum of RNA modifications.

Main Methods:

  • Utilizing high-throughput sequencing methodologies.
  • Employing modification-specific reagents like antibodies and enzymes coupled with next-generation sequencing.
  • Leveraging nanopore sequencing technologies for direct mapping of native RNA modifications.

Main Results:

  • Nanopore technology has enabled the detection of several key RNA modifications (m 6 A, Ψ , I).
  • The signal modulations induced by most RNA modifications remain largely undetermined.
  • Current understanding of the epitranscriptome is limited by technical biases.

Conclusions:

  • A concerted global effort is essential to determine the signatures of all RNA modifications.
  • Characterizing these signatures will mitigate technical biases and advance epitranscriptome research.
  • Comprehensive understanding of the epitranscriptome is critical for fully grasping gene expression regulation.