Insurance contracts, loan agreements, and scientific studies; while it’s easy to pretend that we know what´s going on after a quick skim, we often require a detailed interpretation of the complex combinations of letters, numbers, symbols, and accents to gain a fuller comprehension of the matter at hand.
In the realm of our epitranscriptomic language, years of research has uncovered a range of RNA modifications, including N1-methyladenosine (m1A), that gladly complicate our comprehension. To decipher the complex meaning of the epitranscriptome, studies have employed a plethora of advanced techniques to profile the location and abundance of epitranscriptomic modifications and delineate regulatory pathways. A study using quantitative mass spectrometry (LC-MS/MS) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) obtained a “ball-park” idea of m1A abundance and location, and when combined with other findings, led to the understanding that the m1A modification maintains the structure and function of non-coding RNA (ncRNA) and messenger RNA (mRNA) and promotes translation.
To assess the precise location and further decipher the regulation of m1A, researchers from the laboratory of Chengqi Yi (Peking University, Beijing, China) now describe an intricate new approach: single-base resolution misincorporation-assisted profiling of m1A, or m1A-MAP.
Employing this new technique, Li et al. analyzed the location of m1A throughout the transcriptome of human embryonic kidney cells (HEK293T) and discovered that:
- Of 740 m1A modifications detected, 473 sites locate to mRNAs and lncRNAs
- The majority of m1A occurs in the 5′ untranslated region (UTR) and correlates to increased translation efficiency
- m1A also labels a small subset (53) of transfer RNA (tRNA)-like sites, which are evenly distributed in the transcriptome and require transfer RNA methyltransferase activity (TRMT6/61A)
- Additionally, mitochondrial-encoded transcripts also display enrichment for m1A
- For these mitochondrial mRNAs, m1A in the coding sequence inhibits translation
- Manipulation of m1A levels via a mitochondrial m1A methyltransferase (TRMT61B) confirmed that m1A interferes with translation of mitochondrial mRNA
The authors hope that this intricate and highly detailed study will provide a highly useful resource towards deciphering the specificities behind the m1A modification of mRNA.
To further your understanding of the meaning of m1A in our epitranscriptomic language, read the full story over at Molecular Cell, October 2017.