Ph.D. University of Texas Southwestern Medical Center at Dallas
Neurons receive thousands of synaptic connections from others and modify the strength of individual synapses independently with varying degrees of stability. This experience-dependent synaptic plasticity underlies the molecular and cellular basis of learning and memory. Regulated local translation allows for remote control of gene expression to concentrate proteins in subcellular compartments such as synapses and is important for synaptic plasticity and memory. Thus, we study cytoplasmic polyadenylation element binding proteins (CPEBs), which regulate the translation of target mRNAs for memory and other physiological functions.
Several chemical modifications in mRNAs have been identified to regulate posttranscriptional gene expression. However, the mechanisms underlying epitranscriptome-controlled translation remain largely unexplored. Thus, we also investigate the molecular and physiological functions of cap methyltransferases (CMTRs). Eukaryotic mRNAs are 5'-end capped with a 7-methylguanosine (m7GpppNN, N: any nucleotide), which is important for processing, transport, and translation of mRNAs. The cap structure in higher eukaryotes is further methylated at the 2'-O-ribose position of the first and second nucleotides by CMTR1 and CMTR2. The cap1 structure (m7GpppNmN) is generally believed to mask mRNAs from innate immune surveillance. However, we found that CMTR1-catalyzed 2'-O-methylation is important for gene regulation and brain development independent of silencing innate immunity.
CPEB and translational control by cytoplasmic polyadenylation: impact on synaptic plasticity, learning, and memoryMolecular Psychiatry, May 02, 2023
Dysregulated proteostasis network in neuronal diseasesFrontiers in Cell and Developmental Biology, Feb 24, 2023