A research team from the University of Michigan has published findings in Stem Cell Reports indicating that RNA chemical modifications play a regulatory role in the process of stem cells differentiating into retinal cells. The study focuses on the function of the METTL3 protein, which adds methyl groups to RNA molecules. Using genetic tools, the researchers found that METTL3 in the cell nucleus is a key driver of retinal cell formation.

The research team employed GLORI technology to map all METTL3-modified regions in RNA and combined this data with RNA engineering. They discovered that RNA modifications influence the stem cell-to-retina conversion process by regulating the RNA stability of the Six3 gene. Through an RNA-specific CRISPR system, the researchers confirmed that modifications at the 3' end of RNA molecules are crucial for Six3 gene expression. Experimental data also showed that inhibiting the Ythdf gene family produces a blocking effect similar to METTL3 deficiency.

Senior author Dr. Rajesh C. Rao, Professor of Ophthalmology and Visual Sciences, stated: "This is the first report studying RNA epigenetic mechanisms—how chemical modifications in RNA affect the process of stem cells developing into retinal tissue." The study also found that METTL3 influences RNA function without altering DNA structure, a phenomenon that caught the team's attention.

The research team is currently delving deeper into the connection between RNA modification mechanisms and retinal diseases. Rao added: "We know RNA modifications can be affected by high glucose levels. The retina is a highly sensitive tissue that is easily damaged in diabetic patients, and we want to understand if RNA modifications are involved." This research provides new directions for constructing transplantable cells and treating retinal diseases.