mRNA Stability Is Regulated By Dynamic m6A RNA Methylation

Messenger RNA (mRNA) is a single-stranded RNA molecule that is essential in mediating the transfer of genetic information from DNA by serving as a template for protein synthesis. There are several mechanisms involved in regulating the stability of messenger RNA to influence the level and timing of protein production.  Such mechanisms include regulatory elements such as sequence elements or structural motifs that can target mRNA for degradation.

Furthermore, post-transcriptional modifications such as dynamic methylation of mRNA could also be involved in the regulatory process. One such post-transcriptional modification is the methylation of adenosine at the N6 position to form N6-methyladenosine (m⁶A) in mRNA. The recent discovery of m⁶A demethylases suggests a potentially important role for this modification in the control of mRNA metabolism.  Proteins from the YTH family (YTHDF2 and YTHDF3) have been found to selectively bind m⁶A in mammals and exert regulatory functions. Researchers at the University of Chicago sought to shed more light on the function of the m⁶A modification and establish the role of the YTHDF2 protein in RNA regulation.

Using techniques including photoactivatable ribonucleoside crosslinking and immunoprecipitation (PAR-CLIP) and RNA immunoprecipitation sequencing (RIP-seq), the authors show that m⁶A is selectively recognized by the YTHDF2 “reader” protein to regulate RNA degradation.  This work further contributes to our understanding of the functional significance of the m⁶A modification in RNA as a way to regulate translational potential via mRNA metabolism.