Jonathan Warner, Ph.D

 

Buchler Professor of Transgenic Medicine Department of Cell Biology Chanin Bldg. Room 413   718 430-3022 warner @aecom.yu.edu Biosketch Symposium pix for alums

Research interests The Economics of Ribosome Biosynthesis The ribosome is a molecular machine composed of 4 RNA molecules and 78 different proteins. The construction of a ribosome involves the integration of fundamental cellular processes: the transcription and processing of ribosomal RNA, the transcription, processing and translation of the mRNAs for ribosomal proteins, the assembly of the ribosomal proteins with the ribosomal RNAs, etc. In the yeast Saccharomyces cerevisiae, the synthesis of ribosomes consumes an extraordinary proportion of the cell's resources, accounting for >70% of all transcription, about 50% of all Pol II transcription, and >90% of all pre-mRNA splicing. We have used the genetic/biochemical approaches uniquely available in this organism to study the multiple levels of regulation that control this process. Our current research emphasizes two aspects of ribosome synthesis that will contribute to our understanding of the fundamental aspects of cell growth and regulation: 1) Co-ordinate regulation: One of the biologically interesting aspects of ribosome biosynthesis is that the 78 ribosomal proteins, encoded in 137 genes, must be provided in equimolar amounts with each other, and with rRNA. Amounts count! Overexpression of a given ribosomal protein is frequently deleterious to cell growth; underexpression will limit the production of ribosomes. One of our key questions currently is how this high degree of co-ordinate production is carried out. We, and others, have shown that most, BUT NOT ALL, of the RP genes are transcribed under the control of three proteins, Rap1, Fhl1, and Ifh1. Interestingly, Ifh1p, which is likely to be the transcriptional activating factor, is also found as a complex with proteins that are known to be involved with rRNA transcription and processing. We hypothesize that this interaction is the link that couples rRNA transcription with RP gene transcription, an absolutely critical function for efficient cell growth. Current experiments are aimed to test this hypothesis. 2) Quality Control and Degradation: We recently showed that the insufficient supply of a single ribosomal protein can have a strong effect on the regulation of ribosome synthesis. This led us to realize that the partial deficiency of a single ribosomal protein must lead to the production of many defective ribosomes which must be (A) detected and (B) degraded. Little is known about either process, although the exosome (for the RNA) and the proteosome (for the protein) are likely candidates. We are using Synthetic Genetic Analysis (SGA) to determine the proteins involved in each process, and to understand the biochemical and biological basis of the extreme balance that ribosome synthesis implies.

Recent publications Warner, J. R., Nascent Ribosomes Cell 107, 133-136, 2001 <Abstract> Warner, J. R. and P. M. Knopf, The Discovery of Polyribosomes TiBS 27, 376-380, 2002  Zhao, Y., J.H. Sohn & J.R. Warner, Autoregulation in the Biosynthesis of Ribosomes Molec. Cell. Biol. 23, 699-707, 2003 <Abstract> Rudra, D. & J.R.Warner What Better Measure than Ribosome Synthesis? Genes & Dev., 18, 2431-2436, 2004.  Rudra, D., Y. Zhao, & J.R. Warner, Central Role of Ifh1p-Fhl1p Interaction in the Synthesis of Yeast Ribosomal Proteins, The EMBO Journal, 24, 533-542, 2005 <Abstract> Zhao, Y., K.B. McIntosh, D. Rudra, S. Schawalder, D. Shore, & J.R. Warner Fine-Structure Analysis of Ribosomal Protein Gene Transcription, Molec. Cell. Biol. 26, 4853-4862, 2006 <Abstract> Rudra, D., J. Mallick, Y. Zhao, & J.R. Warner Potential Interface Between Ribosomal Protein Production and pre-rRNA Processing Molec. Cell. Biol. 27, 4815-4824, 2007 McIntosh KB, Warner JR. Yeast ribosomes: variety is the spice of life. Cell. 2007 Nov 2;131(3):450-1. (Preview)

Jonathan Warner: Research interests | Biosketch Faculty research at a glance Birshtein | Bouhassira | Edelmann | Fyodorov | Keogh | Kielian | Kitsis | Nathenson | Query Scharff | Schildkraut | Shafritz | Singer | Skoultchi | Stanley | Steidl |Warner | Ye   Home