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JOAN A. STEITZ

Non-coding RNAs: Roles in Gene Expression

Non-coding (nc)RNAs complexed with proteins to form ncRNPs contribute to every step in gene expression. We concentrate on ncRNPs of the nucleus, 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 deposition of the exon junction complex (EJC), and how early steps in microRNA biogenesis are regulated at the level of the components of the Microprocessor, Drosha and DGCR8. We have found that microRNA processing is more efficient if longer precursors within the cell nucleus remain associated with the chromatin from which they are transcribed.

Some primate herpesviruses [Epstein-Barr virus (EBV), Herpesvirus saimiri (HVS), and Kaposi sarcoma virus (KSHV)] encode ncRNAs that associate with host cell proteins to form ncRNPs. Recent investigations have revealed that one of the HSURs (U-snRNAs) of HVS downregulates a cellular microRNA, MiR-27, by binding and inducing its decay. HVS encodes 6 microRNAs, whose processing is noncanonical and linked to HSUR (snRNA) biogenesis. An RNA element (the ENE) in the PAN RNA of KSHV counteracts a rapid nuclear RNA decay pathway by clamping PAN’s polyA tail in an RNA triplex; PAN RNA is required for late viral protein synthesis and virus production. Our structural studies have allowed identification of putative ENE-like elements in other viral and host ncRNAs, which are being studied. The role of EBV-encoded microRNAs in regulating host and viral apoptotic proteins is being investigated. Proteomics and a cross-linking/deep sequencing procedure (HiTS/CLIP) are being used to elucidate the mechanism by which EBER1 and 2 (abundant ncRNAs) enhance the tumorigenesis of EBV-transformed cells.

Selected Publications

Pawlicki, J. and Steitz, J.A. (2008). Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production. J. Cell Biol. 182, 61-76. PMCID: PMC2447899

Tycowski, K.T., M.-D. Shu, Kukoyi, A., and Steitz, J. A. (2009). A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. Molec. Cell 34, 47-57. PMCID: PMC2700737

Cazalla, D., Yario, T., and Steitz, J.A. (2010). Downregulation of a host microRNA by a Herpesvirus saimiri noncoding RNA. Science 328,1563-1566. PMCID: PMC3075239

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

Alexandrov, A., Colognori, D., and Steitz, J.A. (2011). 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.

Last Updated 07/21/11 myc