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BIOGRAPHY:
Dr. Michaeli earned her Ph.D. in microbiology from Tel-Aviv University in 1985. She then did postdoctoral work until 1990 at the University of California in San Francisco and Berkeley. From 1990 to 1999 she worked at the Weizmann Institute of Science in Rehovot, Israel. She has received the Clore Prize for Excellence, the Moshe Shilo Prize, and most recently in 1999 the Andre Lwoff Prize from the Pasteur-Weitzman Council and French Academy of Science. Currently, she holds a position as Associate Professor of the Life Sciences Department of Bar-Ilan University in Israel. Dr. Michaeli is working on a project entitled "Trans-Splicing and Protein Translocation in Trypanosomes."
RESEARCH ABSTRACT SUMMARY:
Trans-Splicing and Protein Translocation in Trypanosomes
Our research aims to understand the mechanism and machinery of
trans-splicing and protein translocation mediated by the signal
recognition particle in trypanosomes. Having elucidated many of the SL
RNA–snRNA interactions during trans-splicing, we now focus our
research on RNA-binding proteins and splicing factors and their role in
trans-and cis-splicing, with the goal of identifying
trans-splicing–specific factors. Silencing by RNAi of Sm
proteins that bind to the sn and SL RNA demonstrates that these
proteins are essential for both splicing reactions and for the
stability of the U snRNAs. Surprisingly, SL RNA that accumulated in the
cytoplasm during Sm silencing lacked the fourth unique cap nt. Our data
suggest that SL RNA biogenesis involves a cytoplasmic phase and that
the unique cap nts may have a role in export and import of the SL RNA
during this complicated pathway. Interestingly, the SL RNA that
accumulated in the Sm-silenced cells carried the unique pseudouridine
at position –12. By silencing the SLA1 using snoRNAi, an RNAi-related
mechanism that we recently discovered, we showed that the
trypanosome-specific small RNA SLA1 guides this modification. We are
currently investigating the role of this modification for the function
of the SL RNA. To further understand how the SL RNP is brought to the
spliceosome, we tagged in vivo splicing factors and silenced numerous
splicing factors. Our results suggest that the SL RNP is brought to the
spliceosome via its association with the hexameric snRNP complex.
In the protein translocation project, we demonstrated by purifying
the SRP to homogeneity that the trypanosome SRP complex is the first
eukaryotic complex that lacks the Alu-domain binding proteins.
Silencing the chaperone and the SRP pathways suggests that membrane
protein translocation is dependent on the SRP pathway, whereas signal
peptide–containing proteins can transverse the ER membrane also by the
chaperone pathway.
Photo: Kent Kallberg, Kallberg Studios
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