Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine

YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA

“…Our current understanding of m 6 A-mediated cytoplasmic mRNA regulation mainly came from functional and structural studies of YTHDF1 and YTHDF2 [12,13,18,[23][24][25]. However, the role of YTHDF3, another cytoplasmic reader of the m 6 A modification, remains unclear.…”

m6A: Signaling for mRNA splicing

“…So far only a handful of mRNA m 6 A readers are identified and have been implicated in splicing, stability and translation. 5,13,[15][16][17][18][19][20]26 Given the ubiquitous nature of m 6 A modification throughout different types of transcripts, there shall be more m 6 A binding proteins that are worthy of further investigation. Identification of such readers and further elucidation of their effect on the RNA metabolism will definitely expand our current understanding of the potential significance of m 6 A modification.…”

“…Biochemical and biophysical investigations have shown that the aromatic cage formed by tryptophan residues are critical for the recognition of m 6 A in RNA by YTH domain containing proteins. 13 Humans have five YTH domain containing proteins named YTHDC1-2, and YTHDF1-3. YTHDC1 is nuclear m 6 A reader reported to bind to m 6 A through its tryptophan residues at 377 and 428 positions by forming aromatic cage.…”

Update: Mechanisms Underlying N 6 -Methyladenosine Modification of Eukaryotic mRNA

“…1). In agreement, while biochemical and structural analysis revealed YTH as a general RNA binding domain [76], kinetic analysis demonstrated that the binding affinity between YTH domains to m 6 A-modified RNA is 10 times higher than that to non-m 6 A RNA [77, 78]. Furthermore, PAR-CLIP analysis of YTHDF1, YTHDF2 and YTHDC1 identified genome-wide YTH protein binding sites overlapping with the RRACH motif [34, 73, 74].…”