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14 results on '"Bullard, Whitney"'

2. Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection

Author

Yaron, Jordan R., Ambadapadi, Sriram, Zhang, Liqiang, Chavan, Ramani N., Tibbetts, Scott A., Keinan, Shahar, Varsani, Arvind, Maldonado, Juan, Kraberger, Simona, Tafoya, Amanda M., Bullard, Whitney L., Kilbourne, Jacquelyn, Stern-Harbutte, Alison, Krajmalnik-Brown, Rosa, Munk, Barbara H., Koppang, Erling O., Lim, Efrem S., and Lucas, Alexandra R.

Published
2020
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6. Identification of murine gammaherpesvirus 68 miRNA-mRNA hybrids reveals miRNA target conservation among gammaherpesviruses including host translation and protein modification machinery

Author

Bullard, Whitney L., primary, Kara, Mehmet, additional, Gay, Lauren A., additional, Sethuraman, Sunantha, additional, Wang, Yiping, additional, Nirmalan, Shreya, additional, Esemenli, Alim, additional, Feswick, April, additional, Hoffman, Brett A., additional, Renne, Rolf, additional, and Tibbetts, Scott A., additional

Published
2019
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13. A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In VivoTo Promote Latent Infection of Germinal Center B Cells

Author

Wang, Yiping, Feldman, Emily R., Bullard, Whitney L., and Tibbetts, Scott A.

Abstract

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies. In vivo, these viruses infect B cells and manipulate B cell biology to establish lifelong infection. To accomplish this, gammaherpesviruses employ an array of gene products, including miRNAs, short noncoding RNAs that bind to and repress protein synthesis from specific target mRNAs. The in vivorelevance of repression of targets of gammaherpesvirus miRNAs remains highly elusive. Here, we identified a murine gammaherpesvirus miRNA as critical for in vivoinfection and validated the host mRNA EWSR1(Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using a novel technology, we demonstrated that repression of EWSR1was essential for in vivoinfection of the critical B cell reservoir. These findings provide the first in vivodemonstration of the significance of repression of a specific host mRNA by a gammaherpesvirus miRNA.

Published
2019
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14. JBP1 and JBP2 Proteins Are Fe2+/2-Oxoglutarate-dependent Dioxygenases Regulating Hydroxylation of Thymidine Residues in Trypanosome DNA.

Author

Cliffe, Laura J., Hirsch, Gwen, Jin Wang, Ekanayake, Dilrukshi, Bullard, Whitney, Muhan Hu, Yinsheng Wang, and Sabatini, Robert

Subjects
*HYDROXYLATION, *DIOXYGENASES, *PROTEINS, *THYMINE, *THYMIDINE, *GENETIC mutation, *GENE expression
Abstract

We have recently demonstrated that O-linked glucosylation of thymine in trypanosomeDNA(base J) regulates polymerase II transcription initiation. In vivo analysis has indicated that base J synthesis is initiated by the hydroxylation of thymidine by proteins (JBP1 and JBP2) homologous to the Fe2+/2-oxoglutarate (2-OG)-dependent dioxygenase superfamily where hydroxylation is driven by the oxidative decarboxylation of 2-OG, forming succinate and CO2. However, no direct evidence for hydroxylase activity has been reported for the JBP proteins. We now demonstrate recombinant JBP1 hydroxylates thymine specifically in the context of dsDNA in a Fe2+-, 2-OG-, and O2-dependent manner. Under anaerobic conditions, the addition of Fe2+ to JBP1/2-OG results in the formation of a broad absorption spectrum centered at 530 nm attributed to metal chelation of 2-OG bound to JBP, a spectroscopic signature of Fe2+/2-OG-dependent dioxygenases. The N-terminal thymidine hydroxylase domain of JBP1 is sufficient for full activity and mutation of residues involved in coordinating Fe2+ inhibit iron binding and thymidine hydroxylation. Hydroxylation in vitro and J synthesis in vivo is inhibited by known inhibitors of Fe2+/2-OG-dependent dioxygenases. The data clearly demonstrate the JBP enzymes are dioxygenases acting directly on dsDNA, confirming the two-step J synthesis model. Growth of trypanosomes in hypoxic conditions decreases JBP1 and -2 activity, resulting in reduced levels of J and changes in parasite virulence previously characterized in the JBP KO. The influence of environment upon J biosynthesis via oxygen-sensitive regulation of JBP1/2 has exciting implications for the regulation of gene expression and parasite adaptation to different host niches. [ABSTRACT FROM AUTHOR]

Published
2012
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