Ph.D., Harvard University, 2005
B.S.A., Univeristy of Arizona, 2000
Mechanisms and regulation of RNA modifications in post-transcriptional regulation
Making use of genomic, bioinformatic, and systems biology approaches with molecular genetic and biochemical techniques we are identifying and characterizing additional components required for the metabolism and function of various RNA chemical modifications including N6-methyladenosine and NAD+ caps. Specifically, our lab is taking a genetic approach using the model genetic organism Arabidopsis thaliana to identify new factors involved in the writing, erasing, and reading of these chemical additions to RNA molecules, while also uncovering the functionalities of these covalent additions in post-transcriptional regulation of the plant transcriptome during normal development as well as various stress responses. Furthermore, as these pathways are highly conserved, we are also studying these RNA modifications in animal models. The findings from this work will allow a better understanding of how RNA modifications function, and the ways they can be manipulated for controlling gene expression across eukaryotic systems.
Using high-throughput sequencing to study RNA secondary structure and RNA-protein interactions globally
We have pioneered the development of high-throughput, sequencing-based approaches to simultaneously study RNA secondary structure and RNA-protein interactions on a global scale. To do this, we have married classical nuclease-based structure mapping techniques with high-throughput sequencing technology to interrogate the protein binding profile and pairing status of all nucleotides in the RNA molecules of eukaryotic organisms. We believe that the findings from these approaches highlight the importance of RNA-protein interactions and RNA secondary structure in eukaryotes and present an approach that should be widely applicable for the analysis of these key features in any and all organisms.
We are also using these approaches to identify all small (sm)RNA-producing substrates of RNA-DEPENDENT RNA POLYMERASEs (RDRs). More specifically, we use the combination of transcriptome-wide double-stranded (dsRNA) and small RNA sequencing to interrogate the substrates of this class of enzymes in eukaryotes. We are currently characterizing the RDRs of Arabidopsis thaliana.
BIOL 4231: Genome Sciences and Genomic Medicine
BIOL 6010: Communication for Biologists
Prall, W., Sheik, A., Bigeard, J., Bazin, J., Almeida-Trapp, M., Crespi, M., Hirt, H., and Gregory, B.D. 2023. Pathogen-induced m6A dynamics affect plant immunity. Plant Cell 35: 4155-4172.
Sharma, B., Prall, W., Bhatia, G., and Gregory, B.D. 2023. The diversity and functions of plant RNA modifications: what we know and where do we go from here. Annu. Rev. Plant Biol. 74: 53-85.
Prall, W., Ganguly, D.R., and Gregory, B.D. 2023. The covalent nucleotide modifications within plant mRNAs: what we know, how we find them, and what should be done in the future. Plant Cell 35: 1801-1816.
Yu, X., Vandivier, L.E., Willmann, M.R., Trefely, S., Kramer, M.C., Guo, R., Snyder, N.W., and Gregory, B.D. 2021. Messenger RNA 5’ NAD+ capping is a dynamic regulatory epitranscriptome mark that is required for proper response to abscisic acid in Arabidopsis. Dev. Cell 56: 125-140.
Anderson, S.J., Kramer, M.C., Gosai, S.J., Yu, X., Vandivier, L.E., Nelson, A.D.L., Anderson, Z.D., Beilstein, M.A., Fray, R.G., Lyons, E., and Gregory, B.D. 2018. N6-methyladenosine inhibits local ribonucleolytic cleavage to stabilize messenger RNAs in Arabidopsis. Cell Rep. 25: 1146-1157.
Foley, S.W., Gosai, S.J., Wang, D., Selamoglu, N., Solitti, A.C., Koster, T., Steffen, A., Lyons, E., Daldal, F., Garcia, B.A., Staiger, D., Deal, R.B., and Gregory, B.D. 2017. A global view of RNA-protein interactions identifies post-transcriptional regulators of root hair cell fate. Dev. Cell 41: 204-220.
Yu, X., Willmann, M.R., Anderson, S.J., and Gregory, B.D. 2016. Genome-wide mapping of uncapped and cleaved transcripts reveals a role for the nuclear messenger RNA cap-binding complex in plant co-translational RNA decay. Plant Cell 28: 2385-2397.
Vandivier, L.E., Campos, R., Kuksa, P.P., Silverman, I.M., Wang, L.S., and Gregory B.D. 2015. Chemical modifications mark alternatively spliced and uncapped messenger RNAs in Arabidopsis. Plant Cell 27: 3024-3037.
Gosai, S.J., Foley, S.W., Wang, D., Silverman, I.M., Selamoglu, N., Nelson, A.D.L., Beilstein, M.A., Daldal, F., Deal, R.B., and Gregory, B.D. 2015. Global analysis of the RNA-protein interaction and RNA secondary structure landscapes of the Arabidopsis nucleus. Mol. Cell 57: 376-388.
Silverman, I.M., Li, F., Alexander, A., Goff, L., Trapnell, C., Rinn, J.L., and Gregory, B.D. 2014. RNase-mediated protein footprint sequencing reveals protein-binding sites throughout the human transcriptome. Genome Biol. 15: R3.
Li, F., Zheng, Q., Ryvkin, P., Dragomir, I., Desai, Y., Aiyer, S., Valladares, O., Yang, J., Bambina, S., Sabin, L.R., Murray, J.I., Lamitina, T., Raj, A., Cherry, S., Wang, L.S., and Gregory, B.D. 2012. Global analysis of RNA secondary structure in two metazoans. Cell Rep. 1: 69-82.