Joan A Steitz PhD
Sterling Professor of Molecular Biophysics and Biochemistry; Investigator, Howard Hughes Medical Institute
Research Interests
Autoantibodies; Gene Expression; RNA; RNA Processing; SnRNPs; Viral Transformation
Research Summary
Noncoding RNA-protein complexes (ncRNPs) are ubiquitous in eukaryotic cells and inhabit specific cellular compartments. The most famous noncoding nuclear RNPs(snRNPS) participate in pre-mRNA splicing by recognizing important intronsignals and assembling to form an active splicing complex called aspliceosome. There are many other kinds, including those where the RNA is made by an infecting virus. Our recent contributions to understanding the roles of ncRNA-protein complexes in mammalian gene expression include: 1) The discovery that splicing-like snRNPs are made by a virus to degrade a host microRNA. 2) Finding that a viral noncoding RNA possesses an element that forms a triple helix with the polyA tail that serves to stabilize the RNA in the nucleus.
Extensive Research Description
RNA-Protein Complexes: Roles in Gene Expression
Noncoding RNAs are important for every step of gene expression. We concentrate on nuclear noncoding RNAs complexed with proteins, where the most famous small nuclear RNPs (snRNPs) participate in pre-mRNA splicing. Current efforts are aimed at understanding how splicing influences downstream events in gene expression via the exon junction complex (EJC), how guide RNAs modify the snRNA components of snRNPs, and how microRNA biogenesis is regulated during the nuclear maturation steps. Some primate herpesviruses [Epstein-Barr virus (EBV), Herpesvirus saimiri (HVS), and Kaposi sarcoma virus (KSHV)] produce noncoding RNAs that associate with host cell proteins to form snRNPs. Recent investigations have studied the protein binding and nuclear localization of the EBERs of EBV, have revealed that the HSURs of HVS serve to upregulate genes that are hallmarks of T-cell activation in latently infected T cells — in part by binding and accelerating decay of a particular host microRNA, and have characterized an RNA element in the PAN RNA of KSHV that counteracts a rapid nuclear RNA decay pathway and solved its high resolution structure, revealing its mechanism of action. Viral microRNA biogenesis and function are also being studied.
Selected Publications
- Riley, K.J., Yario, T., and Steitz, J.A. (2012). Association of Argonaute proteins and microRNAs can occur after cell lysis. RNA 18, 1581-1585. PMCID: PMC3425773
- Tycowski, K.T., Shu, M.-D., Borah, S., Shi, M., and Steitz, J.A. (2012). Conservation of a triple-helix-forming RNA stability element in noncoding and genomic RNAs of diverse viruses. Cell Reports 2, 26-32. PMCID: PMC3430378
- Cazalla, D., Xie, M., and Steitz, J.A. (2011). A primate Herpesvirus uses the Integrator complex to generate viral microRNAs. Molec. Cell. 43, 982-992.
- Mitton-Fry, R.M., DeGregorio, S.J., Wang, J., Steitz, T.A., and Steitz, J.A. (2010). Poly(A) tail recognition by a viral RNA element through assembly of a triple helix. Science 330, 1244-1247. PMCID: PMC3074936
- Borah, S., Darricarrère, N., Darnell, A., Myoung, J., and Steitz, J.A. (2011). A viral nuclear noncoding RNA binds re-localized poly(A) binding protein and is required for late KSHV gene expression. PLoS Pathogens, In press
- Martinez, I., Cazalla, D., Almstead, L., Steitz, J.A., and DiMaio, D. (2011). miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc. Natl. Acad. Sci., USA 108, 522-527. PMCID: PMC3021067
- Alexandrov, A., Colognori, D., and Steitz, J.A. (2011). Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes Dev. 25, 1078-1090. PMCID: PMC3093123
- Cazalla, D., and Steitz, J.A. (2011). Down-regulation of a host microRNA by a viral noncoding RNA. Nuclear Organization & Function (Cold Spring Harbor Symposia on Quantitative Biology LXXV). pp. 321-324. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
- Riley, K.J-L., Rabinowitz, G.S., and Steitz, J.A. (2010). Comprehensive analysis of rhesus lymphocryptovirus microRNA expression. J. Virol. 84, 5148-5157. PMCID: PMC2863793
- Mortensen, R.D., Serra, M., Steitz, J.A., and Vasudevan, S. (2011). Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc. Natl. Acad. Sci., USA 108, 8281-8286 PMCID: PMC3100953
Selected Publications
- Riley, K.J., Yario, T., and Steitz, J.A. (2012). Association of Argonaute proteins and microRNAs can occur after cell lysis. RNA 18, 1581-1585. PMCID: PMC3425773
- Tycowski, K.T., Shu, M.-D., Borah, S., Shi, M., and Steitz, J.A. (2012). Conservation of a triple-helix-forming RNA stability element in noncoding and genomic RNAs of diverse viruses. Cell Reports 2, 26-32. PMCID: PMC3430378
- Cazalla, D., Xie, M., and Steitz, J.A. (2011). A primate Herpesvirus uses the Integrator complex to generate viral microRNAs. Molec. Cell. 43, 982-992.
- Mitton-Fry, R.M., DeGregorio, S.J., Wang, J., Steitz, T.A., and Steitz, J.A. (2010). Poly(A) tail recognition by a viral RNA element through assembly of a triple helix. Science 330, 1244-1247. PMCID: PMC3074936
- Borah, S., Darricarrère, N., Darnell, A., Myoung, J., and Steitz, J.A. (2011). A viral nuclear noncoding RNA binds re-localized poly(A) binding protein and is required for late KSHV gene expression. PLoS Pathogens, In press
- Martinez, I., Cazalla, D., Almstead, L., Steitz, J.A., and DiMaio, D. (2011). miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc. Natl. Acad. Sci., USA 108, 522-527. PMCID: PMC3021067
- Alexandrov, A., Colognori, D., and Steitz, J.A. (2011). Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes Dev. 25, 1078-1090. PMCID: PMC3093123
- Cazalla, D., and Steitz, J.A. (2011). Down-regulation of a host microRNA by a viral noncoding RNA. Nuclear Organization & Function (Cold Spring Harbor Symposia on Quantitative Biology LXXV). pp. 321-324. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
- Riley, K.J-L., Rabinowitz, G.S., and Steitz, J.A. (2010). Comprehensive analysis of rhesus lymphocryptovirus microRNA expression. J. Virol. 84, 5148-5157. PMCID: PMC2863793
- Mortensen, R.D., Serra, M., Steitz, J.A., and Vasudevan, S. (2011). Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc. Natl. Acad. Sci., USA 108, 8281-8286 PMCID: PMC3100953
- Cazalla, D., Yario, T., and Steitz, J.A. (2010). Downregulation of a host microRNA by a Herpesvirus saimiri noncoding RNA. Science 328,1563-1566.
- Pawlicki, J.M., and Steitz, J.A. (2010). Nuclear networking fashions RNA polymerase II transcripts for function. Trends in Cell Biology 20, 52-61. PMCID: PMC2821161
