Base-Resolution Mapping Reveals Distinct m¹A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Gene expression is regulated by post-transcriptional RNA modifications.
• N1-methyladenosine (m1A) is an mRNA modification with largely unknown location and biogenesis.

Purpose of the Study:

• To develop a method for base-resolution m1A profiling.
• To identify distinct classes of m1A modifications in the human transcriptome.
• To investigate the functional roles of m1A in translation and mitochondrial gene expression.

Main Methods:

• Developed a base-resolution m1A profiling technique using reverse transcription.
• Analyzed m1A distribution in the human transcriptome.
• Investigated the role of TRMT6/61A and TRMT61B methyltransferases.
• Studied the impact of m1A on translation efficiency in the cytoplasm and mitochondria.

Main Results:

• Identified distinct classes of m1A methylomes in the human transcriptome.
• m1A modifications in the 5' UTR, especially at the mRNA cap, enhance translation efficiency.
• A subset of m1A modifications exhibit a tRNA-like motif and depend on TRMT6/61A.
• m1A is prevalent in mitochondrial transcripts and interferes with mitochondrial translation via TRMT61B.

Conclusions:

• The study reveals distinct classes of m1A methylome in humans.
• m1A plays diverse roles in regulating gene expression and translation.
• Provides a resource for studying m1A-mediated epitranscriptomic regulation.