Warren R Jelinek

Biosketch / Results /

Warren Jelinek

Professor, Department of Biochemistry and Molecular Pharmacology
Chair - IBC Committee

Contact Info

Address
227 East 30th Street
New York, NY 10016

212/263-5937
Warren.Jelinek@nyumc.org

Research Summary

We seek to identify molecules that act during the pre-commitment period to cause the commitment event of terminal differentiation in murine erythroleukemia cells (MELC). We mutagenized MELC by retroviral insertion and isolated mutants that fail to commit to the terminal erythrodifferentiation program. Repeatedly, and independently, one particular genomic locus was the insertional target in fail-to-commit mutants. We now seek to identify the gene associated with this locus. We identified a novel mammalian protein kinase, which we termed STPK13, whose mRNA declines dramatically during the MELC pre-commitment period. Further investigation demonstrated that the mRNA also fluctuates in abundance during the normal cell cycle. Homologous genes, termed polo and cdc5 have recently been isolated from Drosophila and Saccharomyces cerevisiae, respectively. Analyses of mutants of these genes have revealed a requirement during mitosis for the encoded protein kinase. The cell cycle-associated mRNA fluctuations we observed in mouse cells is conserved in S. cerevisiae and thus has been maintained during at least five hundred million years of evolution; it is expected to be a fundamental mechanism of regulation of the protein kinase. Our recent observations suggest that cell cycle-associated regulation of pre-mRNA splicing plays a central role in the cell cycle-associated fluctuation of the abundance of this mRNA. The decline in STPK13 mRNA abundance during the MELC pre-commitment period is expected to indicate an anticipation by these cells of a halt in cell division associated with the commitment event. We recently identified a protein target of association of the STPK13 protein kinase. It is a highly conserved RNA helicase which also shows cell cycle regulation. Both proteins are potentially good candidates as antimitotic targets.

Research Interests

Terminal Differentiation in Murine Erythroleukemia Cells

Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase
Lake RJ; Jelinek WR. Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase. Molecular & cellular biology. 1993 Dec ;13(12):7793-7801 (6432)

Replication of a plasmid bearing a human Alu-family repeat in monkey COS-7 cells
Johnson EM; Jelinek WR. Replication of a plasmid bearing a human Alu-family repeat in monkey COS-7 cells. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 1986 Jul ;83(13):4660-4664 (57495)

4.5S RNA is encoded by hundreds of tandemly linked genes, has a short half-life, and is hydrogen bonded in vivo to poly(A)-terminated RNAs in the cytoplasm of cultured mouse cells
Schoeniger LO; Jelinek WR. 4.5S RNA is encoded by hundreds of tandemly linked genes, has a short half-life, and is hydrogen bonded in vivo to poly(A)-terminated RNAs in the cytoplasm of cultured mouse cells. Molecular & cellular biology. 1986 May ;6(5):1508-1519 (57536)

Repetitive sequence transcripts and U1 RNA in mouse oocytes and eggs
Kaplan G; Jelinek WR; Bachvarova R. Repetitive sequence transcripts and U1 RNA in mouse oocytes and eggs. Developmental biology (Orlando). 1985 May ;109(1):15-24 (17401)

ANALYSIS OF RNA SPECIES IN MOUSE OOCYTES BY NORTHERN BLOTTING - ACTIN MESSENGER-RNA, U1-RNA, AND ALU SEQUENCES
BACHVAROVA, R; KAPLAN, G; JELINEK, WR. ANALYSIS OF RNA SPECIES IN MOUSE OOCYTES BY NORTHERN BLOTTING - ACTIN MESSENGER-RNA, U1-RNA, AND ALU SEQUENCES [Meeting Abstract]. Journal of cell biology. 1983 ;97(5):A20-A20 (40604)