The Licatalosi lab studies RNA binding proteins and post-transcriptional regulation.
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Gene expression is highly regulated to ensure that the correct proteins are made in the right cell at the right time. RNA-binding proteins (RBPs) are central to this regulation, acting at multiple levels to fine-tune genetic output. In the nucleus, RBPs have important roles in regulating the processing of mRNA precursors (pre-mRNA) into the smaller mRNA forms that serve as templates for protein synthesis. In different cell types and in different stages of development, pre-mRNA processing events can be altered to generate ‘alternative’ mRNAs. Alternative pre-mRNA processing is a major mechanism used to diversify gene expression in different cell types, allowing individual genes to yield multiple alternative mRNAs that encode related proteins with distinct functional properties. In addition to changing protein-coding sequences, alternative processing can alter regulatory elements that affect mRNA stability, cellular localization, and translation efficiency –elements that are recognized by specific RBPs.
The major goal of my lab is to understand how different RBPs regulate gene expression during mouse spermatogenesis. Research in the lab will combine genetic, bioinformatic, biochemical, and high throughput methods to generate transcriptome-wide maps of RBP-RNA interactions and mRNA regulation in specific spermatogenic cell types (from stem cell to gamete).
Yuan, Y, and Licatalosi, D.D. (2014) Decoding alternative mRNAs in the OMIC-age. Invited chapter in The OMICs: Advances in Neuroscience (Oxford University Press).
Sweet, T.J, and Licatalosi, D.D. (2014) 3’end formation and regulation of eukaryotic mRNAs. Invited chapter in Methods in Molecular Biology (Springer Press).
Licatalosi, D.D. (submitted) Roles of RNA binding proteins and post-transcriptional regulation in driving male germ cell development in the mouse. Invited chapter in Advances in Experimental Medicine and Biology: Systems Biology/Genomics of RNA binding proteins (Springer Press).
Licatalosi, D.D., Yano, M., Fak, J.J., Mele, A., Grabinski, S.E., Zhang, C., and Darnell, R.B. (2012) Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev 26, 1626-1642.
Darnell, J.C., Van Driesche, S.J., Zhang, C., Hung, K.Y.S., Mele, A., Fraser, C.E., Stone, E.F., Chen, C.Fak, J.J., Chi, S.W., Licatalosi, D.D., Richter, J.D., and Darnell, R.B. (2011) FMRP blocks ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247-261.
Zhang, C., Frias, M.A., Mele, A., Ruggiu, M., Eom, T., Marney, C.B., Wang, H., Licatalosi, D.D., Fak,J.J., and Darnell, R.B. (2010) Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science 329, 439-443.
Licatalosi, D.D., and Darnell, R.B. (2010) RNA processing and its regulation: global insights into biological networks. Nat Rev Genet 11, 75-87.
Licatalosi, D.D, Mele, A., Fak, J.J., Ule, J., Kayikci, M., Chi, S.W., Clark, T.A., Schweitzer, A.C., Blume, J.E., Wang, X., Darnell, J.C., and Darnell, R.B. (2008) HITS-CLIP yields genome-wide insights into brain alternative RNA processing Nature 456, 464-469.
Licatalosi, D.D., and Darnell, R.B. (2006) Splicing regulation in neurologic disease Neuron 52, 93-101.
Licatalosi, D.D., Gieger, G., Minet, M., Schroeder, S., Cilli, K., McNeil, J.B., and Bentley, D.L. (2002) Functional interaction of yeast pre-mRNA 3’ end processing factors with RNA polymerase II. Mol. Cell. 9, 1101-1111.