home > faculty > steitz

JOAN A. STEITZ

RNA-Protein Complexes: Roles in Gene Expression
RNA-protein complexes (RNPs) are important for every step of gene expression. We concentrate on RNPs of the nucleus, where the most famous small nuclear RNPs (snRNPs) participate in pre-mRNA splicing. Current efforts are aimed at understanding how the exon junction complex (EJC) is deposited after splicing and how its components relate to other nuclear events, how splicing is linked to 3'-end formation of histone mRNAs, which lack polyA tails, employs many of the same factors that are needed for the cleavage and polyadenylation of most mRNAs.

Some primate herpesviruses [Epstein-Barr virus (EBV), Herpesvirus saimiri (HVS), and Kaposi sarcoma virus (KSHV)] encode small 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, and have uncovered an RNA element in the PAN RNA of KSHV that counteracts a rapid nuclear RNA decay pathway and therefore provides a handle for studying a new form of nuclear mRNA surveillance.

We are investigating the roles of both proteins and micoRNAs that bind to the 3' UTR to control mRNA translation, including the surprising finding that proteins considered repressive (such as FXR1 and AGO2) can upregulate translation under certain physiological conditions.  This led to the discovery that microRNAs themselves can direct either repression or activation of translation, dependent on the cell cycle.  Finally, we are studying the biogenesis of microRNAs, which are fashioned from longer precursors within the cell nucleus before trimming and assembly into microRNPs that control translation in the cytoplasm.

Selected Publications

Vasudevan, S. and Steitz, J. A.  AU-rich element-mediated upregulation of translation by FXR1 and Argonaute 2.  Cell 128, 1105-1118 (2007)

Lytle, J. R., Yario, T. A. and Steitz, J. A.  Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR.  Proc. Natl. Acad. Sci., USA 104, 9667-9672 (2007)

Conrad, N. K., Shu, M. -D., Uyhazi, K. E. and Steitz, J. A.  Mutational analysis of a viral RNA element that counteracts rapid RNA decay by interaction with the polyadenylate tail. Proc. Natl. Acad. Sci., USA 104, 10412-10417 (2007)

Friend, K., Lovejoy, A. F. and Steitz, J. A.  U2 snRNP binds intronless histone pre-mRNAs to facilitate U7 snRNP-dependent 3'-end formation. Molec. Cell 28, 240-252 (2007)

Vasudevan, S., Tong, Y. and Steitz, J. A. Switching from repression to activation:  microRNAs can upregulate translation.  Science 318, 1931-1934 (2007)

Last Updated 04-20-08