817C Poster - 13. Neural development and physiology
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Sara Ríos Méndez ¹; Kimberly Rose Madhwani ²; Ámbar Delgado ³; Jennifer Dumouchel ⁴; Kate O'Connor-Giles ^3,5

Affiliations:
1) NIH Post-Baccalaureate Research Education Program (PREP), Brown University, Providence RI; 2) Neuroscience Graduate Training Program, Brown University, Providence, RI; 3) Department of Neuroscience, Brown University, Providence, RI; 4) Molecular Pharmacology & Physiology Graduate Training Program, Brown University, Providence, RI; 5) Carney Institute for Brain Science, Brown University, Providence, RI

Keywords:
c. synaptogenesis; f. neuromuscular junction

The dynamic regulation of global gene expression is required for proper development and function of the nervous system. Emerging work reveals that dysregulation of global gene expression can result in a myriad of neurodevelopmental and degenerative disorders. Specifically, transfer RNAs (tRNAs), which act as adaptors to decode messenger RNA and deliver the correct amino acid to growing polypeptides, undergo a variety of post-transcriptional modifications that are crucial for tRNA folding and stability, thereby ensuring accurate protein synthesis. tRNA methyltransferase 1 (TRMT1) is one of two mammalian orthologs of yeast tRNA methyltransferase, Trm1. TRMT1 dimethylates the guanosine nucleotide at position 26 of most tRNAs to yield the N2,N2-dimethylguanosine (m2,2G) modification. Frameshift mutations in human TRMT1 underlie autosomal recessive intellectual disability in multiple families, suggesting that guanosine-26 demethylation of tRNAs plays an important role in proper neurodevelopment and function. Potentially overlapping roles for TRMT1 and TRMT1-L complicate mammalian studies so we generated a model of TRMT1 in Drosophila, which encodes a single Trm1 homolog. Our preliminary studies suggest a role for TRMT1 in promoting synapse formation. We will report our latest findings on TRMT1’s in vivo role in nervous system development and function. Further study into TRMT1 will provide insight into the important role of tRNA modification in regulating gene expression in the nervous system.