Kevin Czaplinski, PhD
Department of Biochemistry and Cell Biology
Life Science Building, CMM 542
Stony Brook University
Stony Brook, NY 11794-5215
Office telephone: 631-632-8635
Post-transcriptional control of gene expression in the nervous system
In many instances cells rely on post-transcriptional processes to regulate gene expression very rapidly and locally within the cytoplasm. Translation, localization and degradation of messenger RNA (mRNA) within the cytoplasm are all processes that can coordinate to achieve dynamic control of gene expression. Post-transcriptionally induced changes in gene expression are thought to be mediated through the large Ribonucleo-Protein Complexes (RNPs) that form on each mRNA, called mRNPs, but our understanding of how these regulatory units function is poor.
My lab focuses on post-transcriptional control of gene expression, particularly on localization of mRNA within the cytoplasm, one poorly understood component of post-transcriptional regulation. Active localization of mRNA is particularly important to the nervous system where the cell cytoplasm can extend great distances away from the nucleus. At these distances, diffusion of products produced within the cell soma will not suffice to supply proteins to the neuronal cellular periphery that are needed for cell maintenance and function, synaptogenesis and synaptic plasticity. Cells must actively transport these factors to remote locations, and transporting mRNA in neurons is one means to achieve this. Because mRNA is the template for translation, mRNA localization directs protein synthesis to the distal regions of the cytoplasm where the product will function.
Identification of Transport RNPs in Neurons
My studies take complementary approaches to understand the formation and function of RNP complexes involved in localizing mRNA in neurons. To localize mRNA within the cytoplasm, specific cis-acting sequences within an mRNA are recognized by RNA binding proteins to coordinate formation of the RNP. This RNP interacts with the cytoskeleton as well as with membrane associated signaling complexes to achieve translation of the mRNA at the right time and place within the cytoplasm. Many unanswered questions remain about the roles of most of these RNP components. We are performing studies that will examine the roles of the RNA binding proteins as well as the sequence elements involved in localizing mRNA to the processes of neurons. Several neurological diseases including mental retardation involve mis-regulation of mRNA in the cytoplasm and we believe that understanding these mechanisms will lead to novel therapeutic approaches to treat these diseases.
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