Karen Beemon

Karen Beemon

Professor

PhD, University of California, Berkeley

20A Biology East
410-516-7289 | Lab 410-516-8236
klb@jhu.edu

Karen Beemon is a professor in Biology whose research focuses on the role of TERT and microRNAs in oncogenesis, retroviral RNA stability. 

Karen received her PhD from the University of California, Berkeley and went on to do her postdoctoral work both at UC Berkeley and the Salk Institute. 

Retroviral RNA Processing, Avian Leukosis Virus Tumorigenesis, micro-RNAs

My lab studies retroviral gene expression at the post-transcriptional level. An unusual feature of all retroviruses is that their primary RNA transcript is both a major viral mRNA, encoding capsid proteins, and a pre-mRNA. In addition, this unspliced RNA is packaged into viral particles as genomic RNA. We study control of retroviral RNA splicing, stability, and export. We have identified a Negative Regulator of Splicing (NRS) RNA element within the avian retroviral RNA intron, which helps maintain a portion of the primary transcripts as unspliced mRNA and genomic RNA. We are currently exploring the 3D structure of the NRS RNA (see Figure below) and the mechanism of its splicing suppression. The NRS behaves like a defective 5' splice site, binding all of the splicing snRNPs, and interacting with 3' splice sites. It appears to compete with the authentic 5' splice site for interactions with 3' splice sites. While the NRS pseudo-spliceosome contains all of the splicing snRNPs, their arrangement is aberrant. We have observed the pRP8 splicing scaffold protein is not localized in the pseudo-spliceosome. Recently, we have also found that the NRS promotes polyadenylation in vitro.

Inactivating mutations in the NRS of an avian leukosis virus have been associated with rapid-onset chicken lymphomas, involving viral integration into the c-myb locus. These tumors have been characterized by transcriptional profiling. We are also investigating possible additional integration sites. In several tumors, we have found viral integrations upstream of the telomerase reverse transcriptase (TERT) and associated over-expression of TERT and telomerase activity. We are also studying the role of micro-RNAs in tumors. We are identifying targets of miR155 (bic), a micro-RNA that is over-expressed in chicken and human tumors.

In addition, we are exploring the mechanism of nonsense-mediated RNA decay (NMD), induced by premature termination codons in the gag gene of unspliced retroviral RNAs. This is particularly interesting because NMD in higher organisms is thought to be coupled to splicing, and the deposition of exon-junction complexes. We have shown that NMD of unspliced viral RNAs is dependent on Upf1 and translation. Further, we have observed a stability element downstream of the normal gag termination codon. When these downstream sequences are removed, the RNA undergoes NMD. We think these stability sequences may be necessary to stabilize RNAs having a long 3' UTR.

NMR structure of  NRS pseudo-5' splice site

Giles, K.E. and Beemon, K.L. 2005.  Retroviral splicing suppressor sequesters a 3’ splice site in a 50S aberrant splicing complex. Mol Cell Biol. 25:4397-405.

 

Weil, J.E. and Beemon, K.L. 2006.  A 3’ UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus. RNA 12:102-10.

 

Yang, F., Xian, R.R., Li, Y., Polony, T. and Beemon, K.L. 2007.  Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B   cell lymphomas. Proc. Natl. Acad. Sci. USA.  104:18952-7.

 

Bolisetty, M.T., Dy, G., Tam, W., and Beemon, K.L. 2009. Reticuloendotheliosis virus strain T induces microRNA-155, which targets  JARID2 and promotes cell survival. J. Virol. 83:12009-17.

 

Beemon, K.L. and Bolisetty, M. 2010.  Mechanisms of Oncogenesis by Retroviruses in Retroviruses and Insights into Cancer (Dudley, J., ed.) Springer  pp. 31-52. 

 

Bolisetty, M.T. and Beemon, K.L. 2012. Splicing of internal large exons is defined by novel cis-acting sequence elements. Nucleic Acids Res. 40:9244-9254.

 

Bolisetty, M.T., Blomberg, J., Benachenhou, F., Sperber, G., and Beemon, K.L. 2012. Unexpeced diversity and expression of avian endogenous retroviruses. MBio 3(5).  doi:pii: e00344-12.  10.1128/mBio.00344-12. 

 

Withers, J.B., Ashvetiya, T., and Beemon, K.L. 2012. Exclusion of exon 2 is a common mRNA splice variant of primate telomerase reverse transcriptases. PLoS One. 7(10):e48016. doi: 10.1371/journal.pone.0048016.

 

LeBlanc, J., Weil J. and Beemon, K. 2013. Post-transcriptional regulation of retroviral gene expression: primary RNA transcripts play three roles as pre-mRNA, mRNA and genomic RNA.  WIREs RNA 4(5):567-80.

 

Quek, B.L. and Beemon, K. 2014. Retroviral strategy to stabilize viral RNA. Curr. Opinion in Microbiology. 18:78-82.  PMCID:  PMC4020189

 

Justice, J, Malhotra, S, Ruano, M, Li, Y, Zavala, G, Lee, N, Morgan, R and Beemon, K. 2015. The MET gene is a common integration target in avian leucosis virus subgroup J induced chicken hemangiomas. J. Virology, 89(9):4712-9.  PMCID: PMC4403454

 

Justice, JF 4th, Morgan, RW, and Beemon, KL. 2015.   Common viral integration sites identified in avian leukosis virus-induced B-cell lymphomas. mBio. 6(6) pii: e01863-15. doi: 10.1128/mBio.01863-15.

 

 

Ge, Z, Quek, BL, Beemon, KL, and Hogg, JR. 2016. Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway. eLIFE,   Jan 8;5. pii: e11155. doi: 10.7554/eLife.11155.

 

Nehyba, J., Malhotra, S, Winans, S, O’Hare, TH, Justice, J IV and Beemon, K.L.  2016  Avian leukosis virus activation of an antisense RNA upstream of TERT in B-cell lymphomas.  J. Virol. 90: 9509—17.  PMCID: PMC5044821

 

Lam G, Xian RR, Li Y, Burns KH, and Beemon KL. 2016. Lack of TERT promoter mutations in human B-cell non-Hodgkin lymphoma.  Genes (Basel).  7(11). pii:     E93.

 

Winans S, Larue RC, Abraham CM, Shkriabai N, Skopp A, Winkler D, Kvaratskhelia M, Beemon KL. 2017.  The FACT complex promotes avian leukosis virus DNA integration.  J. Virol. 91(7)  pii: JVI.00082-17. doi:          10.1128/JVI.00082-17. PMCID:  PMC5355599

 

Balagopal V. and Beemon KL. 2017. Rous sarcoma virus RNA stability element   inhibits deadenylation of mRNAs with long 3’ UTRs.  Viruses 9(8).  pii: E204. Doi: 10.3390/v9080204.  PMCID:  PMC5580461

 

Winans S, Flynn A, Malhotra S, Balagopal V, and Beemon KL. 2017. Integration of ALV into CTDSPL and CTDSPL2 genes in B-cell lymphomas promotes cell   immortalization, migration and survival.  Oncotarget 8(34):57302-57315.  doi: 10.1863/oncotarget.19328.  PMCID:  PMC5593642

 

Malhotra S, Winans S, Lam G, Justice J, Morgan R, and Beemon K. 2017. Selection for avian leukosis virus integration sites determines the clonal progression of B-cell lymphomas.  PLoS Pathog.  13(11):e1006708.  doi:    10.1371/journal.ppat. 1006708.  PMCID: PMC5687753.

 

Malhotra S, Freeberg MA, Winans SJ, Taylor J, and Beemon KL. 2017. A novel   long non-coding RNA in the hTERT promoter region regulates hTERT expression Non-coding RNA 4, 1; doi:10.3390/ncrna401001.

 

Lam G. and Beemon K.L. 2018. ALV integration-associated hypomethylation at the TERT promoter locus. Viruses 10, 74.  Doi 10.3390/v10020074.  PMCID:   PMC5850381

Postdoctoral Fellows

Scott Johnson

Graduate Students

Gary Lam
Bao Lin Quek

Undergraduate Student

Anthony Gacita

Technician

YingYing Li

BeemonLab