An additional class of m6A readers

Abstract

Abundant N⁶-methyladenosine (m⁶A) mRNA-modification influences mRNA fate by stimulating recruitment of m⁶A reader proteins. A previously unappreciated class of m⁶A reader proteins is now shown to use a common RNA-binding domain and flanking regions to selectively bind m⁶A-containing mRNAs increasing their translation and stability.

Figure 1

Three classes of m⁶A reader proteins. Class I m⁶A reader proteins use a YTH domain (blue) to directly bind the m⁶A base (red). This class includes the five human proteins that contain a YTH domain. Class II m⁶A reader proteins use an m⁶A-switch mechanism to bind m⁶A-containing transcripts: m⁶A modification of RNA destabilizes Watson-Crick base-pairing and increases the accessibility of a single-stranded RNA motif (cyan), which is recognized by the m⁶A reader protein (green). The RNA motif can also overlap with the m⁶A site (not shown for simplicity). This class includes hnRNPC, hnRNPG, and possibly hnRNPA2B1. Class III m⁶A reader proteins use a common RNA binding domain (RBD) and its flanking regions (green) to recognize m⁶A-containing transcripts. This class includes the IGF2BPs, which use KH domains and their flanking regions to selectively bind m⁶A-containing RNAs, and possibly hnRNPA2B1, in which the RRMs and their flanking regions might contribute to m⁶A selectivity.