drach

DRACH is a five-nucleotide RNA sequence motif associated with the installation of N6-methyladenosine (m6A) on eukaryotic mRNA and long noncoding RNA. The motif is written as D-R-A-C-H, where the central A is the methylated residue. The letters D, R, and H are degenerate symbols: D stands for A, G, or U; R stands for A or G; H stands for A, C, or U. The C in the fourth position is invariant. As a result, an m6A site typically occurs within a sequence context such as [A/G/U]-[A/G]-A-C-[A/C/U].

DRACH is not a universal rule but a conserved consensus that describes where methylation by the m6A writer complex tends to occur. The methyltransferase core, primarily METTL3 with METTL14 as a stabilizing partner, writes m6A marks, aided by cofactors such as WTAP, KIAA1429, and RBM15. Reversible demethylation is carried out by erasers like FTO and ALKBH5. Proteins containing YTH or other reader domains recognize m6A and influence RNA processing, export, translation efficiency, and stability.

Biological significance attributed to DRACH-associated m6A includes regulation of splicing, mRNA decay, and translation, with impacts on development, stress responses, and cell differentiation. The motif has facilitated high-throughput mapping of m6A across transcriptomes using techniques such as MeRIP-seq and miCLIP, revealing a bias for DRACH-containing regions near stop codons and 3' untranslated regions in many organisms. Ongoing research continues to refine the understanding of DRACH’s role in gene expression and its variation across tissues and species.