RNA chemical modifications, particularly N6-methyladenosine known as m6A, shape gene expression by altering the fate of messenger RNAs and noncoding RNAs. Mapping efforts led by Yuval Dominissini at the Weizmann Institute and by Samie Jaffrey at Weill Cornell Medicine established the widespread and regulated distribution of m6A across the transcriptome, demonstrating that these marks are not random but concentrated in regions that influence splicing, export, stability, and translation. The relevance to human biology arises from the capacity of m6A and other modifications to modulate protein production rapidly, a feature that connects molecular signaling to organismal responses in development, brain function, and disease.
Molecular actors and mechanisms
The functional logic of RNA modification depends on writer, eraser, and reader proteins. The METTL3 METTL14 complex installs m6A marks while enzymes such as FTO and ALKBH5 can remove them, creating dynamic regulation. Reader proteins with YTH domains bind m6A and direct transcripts toward enhanced translation or accelerated decay, a framework characterized in mechanistic studies by Chuan He at the University of Chicago. These interactions alter ribosome recruitment and RNA-protein assembly, thereby tuning protein output independently of transcriptional changes and enabling rapid adjustments to cellular needs.
Stress responses and physiological impact
Under environmental and cellular stressors, including heat shock and oxidative stress, shifts in RNA modification patterns reprogram translation to favor stress-response proteins, a process documented in work from Samie Jaffrey at Weill Cornell Medicine and Chuan He at the University of Chicago. Such reprogramming preserves proteostasis and supports survival during acute insults, while chronic dysregulation can contribute to disease. Altered expression or mutation of writers, erasers, and readers has been associated with cancer progression and neurological dysfunction in multiple research programs, highlighting impacts on tissue identity and regenerative capacity. Human clinical samples and model systems reveal that modifications provide a layer of regulation that reflects both cellular history and environmental exposures, tying molecular signatures to cultural and territorial patterns of disease prevalence through population studies and translational research efforts.
The distinctiveness of RNA modification lies in its reversible, transcript-selective control over gene output, enabling cells to integrate metabolic state, developmental cues, and external stress into coherent phenotypic outcomes. Evidence from specialized institutions and recognized experts underscores a paradigm in which chemical marks on RNA act as dynamic mediators between genome information and adaptive physiology.
