| Budget Amount *help |
¥130,900,000 (Direct Cost: ¥130,900,000)
Fiscal Year 2006: ¥30,200,000 (Direct Cost: ¥30,200,000)
Fiscal Year 2005: ¥30,200,000 (Direct Cost: ¥30,200,000)
Fiscal Year 2004: ¥23,500,000 (Direct Cost: ¥23,500,000)
Fiscal Year 2003: ¥23,500,000 (Direct Cost: ¥23,500,000)
Fiscal Year 2002: ¥23,500,000 (Direct Cost: ¥23,500,000)
|
|---|
| Research Abstract |
Recent molecular and structural studies including those from this laboratory have revealed that proteins called translation factors mimic the shape of tRNA. One of them, a polypeptide release factor (RF), encodes a tripeptide that serves as an ‘anticodon' to decipher stop codons in mRNA. These findings let us to propose the novel concept of macromolecular mimicry between protein and RNA. Moreover, The [PSI^+] element of budding yeast represents the prion conformation of translation release factor eRF3 that is propagated and transmitted in the cytoplasm. On many levels, yeast prions are analogous to mammalian prions and much interest lies in understanding how prions are able to generate variation in isogenic strains. We have investigated RFs and ribosome-recycling-factor (RRF) from the viewpoint of molecular mimicry and prion transmission, and uncovered the following aspects.
1) Crystal structure and functional domain annotation of S. Pombe eRF3.
2) Functional interplay of EF-G and RRF at
… More
their tRNA-mimicry domains.
3) The critical role of the universally conserved A2602 of 23S rRNA for the peptide-release activity.
4) Part of the prion domain of yeast eRF3 masks the eRF3-binding site in eRF1.
5) The role of ribosomal protein L11 domains for the cooperative interaction with RF1 and RF2, responsible for translation termination.
6) The role of nonprion-state N-terminal domain of yeast eRF3 for functionality and stability of eRF3.
7) RRF disassembles the posttermination ribosomal complex independent of the ribosomal translocase activity of EF-G.
8) Discovery of a novel [PSI^+] prion variant that is independent of Hsp104.
9) Conformational memory preserved in a weak-to-strong or strong-to-weak [PSI^+] conversion during transmission to Sup35 prion variants.
10) The N-terminal 41-residue domain of S. cerevisiae Sup35 is a species-barrier determinant for [PSI^+] prion transmission.
11) Genome-wide screening and genetic selection for factors, including Hsp104 and other novel components, responsible for the maintenance of yeast prions. Less
|
