This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Ytm1, Nop7, and Erb1 are essential, conserved nucleolar proteins necessary for assembly of 60S ribosomal subunits. Each of these three proteins is dependent on the other for their assembly into and stable association with preribosomes. In their absence, processing of 27SA3 pre-rRNA to 27SB pre-rRNA is blocked. Interaction between the central domain of Nop7 with the conserved amino-terminal middle of Erb1 is required for their recruitment into pre-rRNPs. The WD40 motif of Ytm1 then binds to Erb1 amino-terminal to the Nop7 binding site. Consistent with these domains of interaction, expression of truncated Ytm1 or Erb1 constructs containing only these interaction domains enables the proteins to associate with each other, assemble into preribosomes, and cause a dominant negative effect on ribosome biogenesis. What are the functions of the conserved amino-terminal half of Ytm1 or the conserved WD40 motif in the C-terminal half of Erb1, which are missing in these dominant-negative truncations? Erb1 also may function in cell growth and proliferation; overexpression of Erb1 interferes with mitotic chromosome segregation. How does Erb1 participate in this pathway?To address these questions, we are carrying out genome-wide two-hybrid screens using the amino-terminal half of Ytm1, the C-terminal half of Erb1 and full-length Erb1. Interactions of these portions of Erb1 and Ytm1 with other molecules in assembling ribosomes may be critical to establish proper dynamics of ribosome biogenesis.
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