Anna Sherwood
MINDtheCAP: A new role of RNA caps in intellectual disability
MINDtheCAP investigates a newly discovered mechanism that may help explain why some children develop intellectual disabilities. Many children with global developmental delay (GDD) struggle with movement, speech, and learning, and in about half of cases, the genetic cause is unknown.
Recent studies have linked mutations in a gene called NUDT2 to GDD and intellectual disability, but how these mutations affect brain development is unclear.This project focuses on a rare type of molecular tag called an Ap4A cap, found on RNA鈥攖he genetic messages that help cells make proteins.
Normally, NUDT2 removes these caps to regulate RNA stability. When NUDT2 is mutated, these caps may accumulate and disrupt normal brain development. To study this, I developed Ap4A-seq, a new sequencing method that can identify Ap4A-capped RNAs across the entire genome鈥攕omething no existing technique can do.Using neurons grown in the lab, I will compare normal cells to those with patient-derived NUDT2 mutations introduced via CRISPR. I will also test whether restoring NUDT2 function or using a plant-derived enzyme can reverse the RNA changes.
This research could uncover a new layer of gene regulation in the brain and explain how NUDT2 mutations lead to developmental disorders. Ultimately, it may lead to earlier diagnoses and new treatment strategies for affected children.
