Bert L. Semler
Microbiology & Molecular Genetics, School of Medicine
Phone: (949) 824-7573
Email: blsemler@uci.edu
http://www.ucihs.uci.edu/microbio/
http://www.faculty.uci.edu/profile.cfm?faculty_id=2242
Bert Semler
One research focus of Dr. Semler’s laboratory stems from his interest in IRES-mediated translation initiation on viral mRNAs. This mode of translation is also utilized by a limited number of cellular mRNAs whose functions may be required when normal cap-dependent translation is shut down (e.g., during mitosis or in cells undergoing physiological stress). One such mRNA encodes a murine voltage-gated potassium channel, Kv1.4. Potassium channels are known to regulate ion balance, membrane potential, secretion, and cell excitability. The specific mRNA for Kv1.4 is expressed in brain, heart, and skeletal muscle, and there appears to be translational regulation of its expression. They have previously shown that the long (1.2 kb) 5’ noncoding region of Kv1.4 mRNA contains an IRES element that is capable of directing translation initiation. Their research is currently focused on identification of cellular RNA binding proteins that interact with the Kv1.4 IRES and allow this mRNA to bypass the normal requirements for cap-dependent initiation via ribosome scanning. In addition, they are analyzing how the 5’ noncoding region of Kv1.4 may interact with the long 3’ noncoding region of this mRNA to regulate translation. Data from their work should provide new insights into the mechanisms of internal ribosome entry used by specific viral and cellular mRNAs, mechanisms that will ultimately be crucial to understanding of cellular growth control (and its loss in transformed cells) since key cellular regulatory proteins like c-myc, vascular endothelial growth factor (VEGF), and fibroblast growth factor 2 (FGF-2) are all produced from mRNAs harboring IRES elements in their 5’ noncoding regions.
Selected Publications:
Jang, G. M., Leong, L. E., Hoang, L. T., Wang, P. H., Gutman, G. A., and Semler, B. L. (2004). Structurally distinct elements mediate internal ribosome entry within the 5'-noncoding region of a voltage-gated potassium channel mRNA. J Biol Chem 279(46), 47419-30.
Jimenez, J., Jang, G. M., Semler, B. L., and Waterman, M. L. (2005). An internal ribosome entry site mediates translation of lymphoid enhancer factor-1. Rna 11(9), 1385-99.
Bedard, K. M., Daijogo, S., and Semler, B. L. (2007). A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation. Embo J 26(2), 459-67.
Jang, G. M., Tanaka, B. S., Gutman, G. A., Goldin, A. L., and Semler, B. L. (2008). Alternative polyadenylation signals in the 3' non-coding region of a voltage-gated potassium channel gene are major determinants of mRNA isoform expression. Gene 408(1-2), 133-45.
Semler, B. L., and Waterman, M. L. (2008). IRES-mediated pathways to polysomes: nuclear versus cytoplasmic routes. Trends Microbiol 16(1), 1-5. |
