We study post-transcriptional gene regulation by RNA binding proteins. Current research focuses on RNA regulation in response to T cell receptor activation, and developing new tools to study protein-RNA interactions.
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 (in the nucleus and cytoplasm) to fine-tune genetic output.
We use multiple approaches including transcriptome-profiling tools (RNA-Seq, ribosome-profiling, PolyA-Seq, CLIP), bioinformatics, transgenic mouse and cell culture models, flow cytometry, and microscopy. With these tools we aim to get a comprehensive view of RNA regulation and its biological functions in different cell contexts.
Regardless of the biological context, we are generally interested in determining:
- What genes are post-transcriptionally regulated at the RNA level?
- How is RNA regulation achieved?
- How does RNA regulation affect cell phenotype?
The lab is also interested in developing new tools to study protein-RNA interactions.
- Licatalosi DD. Intron removal by the spliceosome: a solo job or a team effort? Molecular Cell (2021) 81, 2275-2277.
- Sharma D, Zagore LL, Brister MW, Crespo-Hernandez CE, Licatalosi DD*, and Jankowsky E*. The kinetic landscape of an RNA binding protein in cells. Nature (2021) 591, 152-156. *co-corresponding authors
- Seachrist DD, Hannigan MM, Ingles NN, Webb BM, Weber-Bonk KL, Yu P, Bebek G, Singh S, Sizemore ST, Varadan V, Licatalosi DD, and Keri RA. The transcriptional repressor BCL11A promotes breast cancer metastasis. Journal of Biological Chemistry (2020).
- Licatalosi DD*, Ye X, Jankowsky E*. Approaches for measuring the dynamics of RNA-protein interactions. WIRES RNA (2019) doi:10.1002/wrna.1565. *co-corresponding authors
- Zagore LL, Akesson, CC, and Licatalosi DD. Efficient GFP-labelling and analysis of spermatogenic cells using the IRG transgene and flow cytometry. Genesis (2019) doi: 10.1002/dvg.23283
- Saito Y, Yuan Y, Zucker-Scharff I, Fak JJ, Tajima Y, Licatalosi DD, and Darnell RB. Neuron-specific cTag-CLIP reveals cell-specific diversity of functional RNA regulation in the brain. Neuron (2019) 101, 707-720.
- Zagore LL, Sweet TJ, Hannigan MM, Weyn-Vanhentenryck S, Zhang C, and Licatalosi DD. Dazl regulates germ cell survival through a network of polyA-proximal mRNA interactions. Cell Reports (2018) 25:1225.
- Hannigan MM, Zagore LL, and Licatalosi DD. Mapping transcriptome-wide protein-RNA interactions to elucidate RNA regulatory programs. Quantitative Biology (2018) 6, 228-238.
- Guenther UP, Weinberg DE, Zubradt MM, Tedeschi FA, Stawicki BN, Zagore LL, Brar GA, Licatalosi DD, Bartel DP, Weissman JS, and Jankowsky E. The helicase Ded1p controls use of near-cognate translation initiation codons in 5'UTRs. Nature (2018) 559, 130-134.
- Herjan T, Hong L, Bubenik J, Bulek K, Qian W, Liu C, Li X, Chen X, Yang H, Ouyang S, Zhou H, Zhao J, Licatalosi DD, Qin J, Cockman E, Komireddy V, Fox P, Hamilton T, Driscoll D, and Li X. Act1 promotes mRNA stabilization via direct binding to a stem-loop motif and disrupting the decapping complex. Nature Immunology (2018) 19, 354-365.
- Hannigan MM, Fujioka H, Brett-Morris A, Mears JA, and Licatalosi DD. PTBP2-dependent alternative splicing regulates protein transport and mitochondria morphology in post-meiotic germ cells. bioRxiv (2018) 497461; doi: https://doi.org/10.1101/497461
- Hannigan MH, Zagore LL, and Licatalosi DD. Ptbp2 controls an alternative splicing network required for cell communication during spermatogenesis. Cell Reports (2017) 19, 2598-2612.
- Licatalosi DD. 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 (2016) 907, 123-151.
- Zagore LL, Grabinski SE, Sweet TJ, Hannigan MM, Sramkoski RM, Li Q, and Licatalosi DD. RNA binding protein Ptbp2 is essential for male germ cell development. Molecular and Cellular Biology (2015) 35, 4030-4042.
- Yuan Y, and Licatalosi DD. Decoding alternative mRNAs in the OMIC-age. Invited chapter in The OMICs: Advances in Neuroscience (2014) (Oxford University Press).
- Sweet TJ, and Licatalosi DD. 3’end formation and regulation of eukaryotic mRNAs. Invited chapter in Methods in Molecular Biology (2014) (Springer Press).
- Sundermeier TR, Jin H, Kleinjan ML, Mustafi D, Licatalosi DD, and Palczewski K. Argonaute High-Throughput Sequencing of RNAs Isolated by Cross-Linking Immunoprecipitation Reveals a Snapshot of miRNA Gene Regulation in the Mammalian Retina. Biochemistry (2014) 53, 5831-5833.
- Licatalosi DD, Yano M, Fak JJ, Mele A, Grabinski SE, Zhang C, and Darnell RB. Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes & Development (2012) 26, 1626-1642.
- Darnell JC, Van Driesche SJ, Zhang C, Hung KYS, Mele A, Fraser CE, Stone EF, Chen C, Fak JJ, Chi SW, Licatalosi DD, Richter JD, and Darnell RB. FMRP blocks ribosomal translocation on mRNAs linked to synaptic function and autism. Cell (2011) 146, 247-161.
- Zhang C, Frias MA, Mele A, Ruggiu M, Eom T, Marney CB, Wang H, Licatalosi DD, Fak JJ, and Darnell RB. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science (2010) 329, 439-443.
- Licatalosi DD, and Darnell RB. RNA processing and its regulation: global insights into biological networks. Nature Reviews Genetics (2010) 11, 75-87.
- Licatalosi DD, Mele A, Fak JJ, Ule J, Kayikci M, Chi SW, Clark TA, Schweitzer AC, Blume JE, Wang X, Darnell JC, and Darnell RB. HITS-CLIP yields genome wide insights into brain alternative RNA processing. Nature (2008) 456, 464-469.
- Licatalosi DD, and Darnell RB. Splicing regulation in neurologic disease. Neuron (2006) 52, 93-101.
- Licatalosi DD, Gieger G, Minet M, Schroeder S, Cilli K, McNeil JB, and Bentley DL. Functional interaction of yeast pre-mRNA 3ʼ end processing factors with RNA polymerase II. Molecular Cell (2002) 9, 1101-1111.
- Smith MD, Licatalosi DD, and Thompson JE. Co-association of cytochrome f catabolites and plastid-lipid-associated protein with chloroplast lipid particles. Plant Physiology (2000) 124, 211-221.
- Yankulov K, Todorov I, Romanowski P, Licatalosi D, Cilli K, McCracken S, Laskey R, and Bentley DL. MCM proteins are associated with RNA polymerase II holoenzyme. Molecular and Cellular Biology (1999) 19, 6154-6163.