Department of Molecular & Cell Biology

Home Faculty and Research Faculty by Name Britt Glaunsinger

Britt Glaunsinger

Associate Professor of Biochemistry, Biophysics and Structural Biology*
*and of Plant and Microbial Biology

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Research Interests

Our interests lie in dissecting how viruses interface with pathways that govern cellular messenger RNA processing and turnover.  Manipulating RNA stability can impact gene expression on a global scale, but is also critical for fine-tuning cellular responses to specific stimuli as well as eliminating flawed and potentially deleterious transcripts.  We seek to pinpoint viral targets within these pathways to better understand mechanisms by which viruses regulate their own messages and/or eliminate competing (or antiviral) cellular transcripts.  We anticipate that these studies will also enhance our understanding of how such important pathways are normally regulated in human cells.

Current Projects

What cellular factors are required to promote global cellular mRNA destruction by γ-herpesviruses?

γ-herpesviruses such as Kaposi’s sarcoma-associated herpesvirus (KSHV) promote global cellular mRNA destruction during their lytic replication cycle.  A critical viral effector of this host shutoff phenotype is called SOX (encoded by ORF37 in KSHV and MHV68). We are conducting both targeted and genome-wide screening experiments to identify cellular factors either directly targeted by KSHV SOX (and its homologs) or involved as downstream effectors of mRNA destruction in SOX-expressing cells.  We are also interested in determining whether the regulation of key mRNA turnover enzymes and pathways is altered during viral infection, and whether these pathways are required for viral replication.  Finally, we are exploring how SOX-induced alterations in RNA processing influence RNA stability, localization, and gene expression in cells.

How does SOX-induced mRNA turnover affect viral transcripts?

KSHV mRNAs look essentially like cellular transcripts; many are spliced, and they are transcribed and processed using cellular machinery.  How does host shutoff affect the stability of these viral mRNAs, and what implications does this have for viral fitness?

What are the mechanisms and consequences of selective escape from mRNA degradation during lytic KSHV infection?

Although the majority of cellular messages are downregulated during KSHV infection, a subset of mRNAs evade destruction.  Using next generation deep sequencing, we are defining the composite of transcripts that are either susceptible or resistant to host shutoff.  This information is being used to explore how RNA sequence and structural elements may confer susceptibility to SOX, and whether RNP complex remodeling occurs on resistant transcripts in cells undergoing host shutoff.

What is the role of host shutoff in the viral lifecycle?

How does enhanced mRNA degradation benefit these viruses?  We are generating viral mutants defective for host shutoff and analyzing their relative replicative success and ability to evade immune destruction both in vitro and in vivo.

Selected Publications

Gaglia M M, Covarrubias S, Wong W, Glaunsinger BA.  2012.  A common strategy for host RNA degradation by divergent viruses. Journal of virology. 86(17):9527-30.

 

Kronstad LM, Glaunsinger BA.  2012.  Diverse virus-host interactions influence RNA-based regulation during γ-herpesvirus infection. Current opinion in microbiology.

 

Covarrubias S, Gaglia MM, Kumar RG, Wong W, Jackson AO, Glaunsinger BA.  2011.  Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1. PLoS pathogens. 7(10):e1002339.

 

Clyde K, Glaunsinger BA.  2011.  Deep sequencing reveals direct targets of gammaherpesvirus-induced mRNA decay and suggests that multiple mechanisms govern cellular transcript escape. PloS one. 6(5):e19655.

 

Richner JM, Clyde K, Pezda AC, Cheng B Y H, Wang T, Kumar RG, Covarrubias S, Coscoy L, Glaunsinger B.  2011.  Global mRNA degradation during lytic gammaherpesvirus infection contributes to establishment of viral latency. PLoS pathogens. 7(7):e1002150.

 

Kumar RG, Shum L, Glaunsinger BA.  2011.  Importin alpha-mediated nuclear import of cytoplasmic poly(A) binding protein occurs as a direct consequence of cytoplasmic mRNA depletion. Molecular and cellular biology. 31(15):3113-25.

 

Clyde K, Glaunsinger BA.  2010.  Getting the message direct manipulation of host mRNA accumulation during gammaherpesvirus lytic infection. Advances in virus research. 78:1-42.

 

Gaglia M and Glaunsinger B. (2010) Viruses and the cellular RNA decay machinery. WIRES RNA 1(1):47-59

 

Glaunsinger B and Lee Y. (2010) How Tails Define the Ending: Divergent Roles for Polyadenylation in RNA Stability and Gene Expression. RNA Biology. Jan 6; 7(1)

Covarrubias S, Richner J, Clyde K, Lee Y, and Glaunsinger B.  (2009) Host Shutoff is a Conserved Phenotype of Gammaherpesvirus Infection and is Orchestrated Exclusively from the Cytoplasm. Journal of Virology. Sep;83(18):9554-66

Lee Y and Glaunsinger B. (2009) Aberrant Herpesvirus-Induced Polyadenylation Correlates With Cellular Messenger RNA Destruction. PLoS Biology.  May 5;7(5):e1000107.

Last Updated 2012-08-16