Abstract
Many eukaryotes encode multiple isoforms of the cap-binding translation initiation factor (eIF4E). Leishmanias and other trypanosomatids encode four paralogs of this protein, but none can complement the eIF4E function in a yeast mutant. A low conservation is observed between the four paralogs, suggesting they assist these organisms survive a multitude of conditions encountered throughout the life cycle. Earlier attempts to decipher their function led to identification of LeishIF4E-4 as the canonical translation initiation factor. LeishIF4E-1 appears to function during thermal stress, via a mechanism not yet understood. LeishIF4E-3 hardly binds cap-4 and is, therefore, less likely to serve as a typical initiation factor. Although it interacts with an eIF4G homolog, LeishIF4G-4, the two polypeptides do not co-migrate on sucrose gradients. While LeishIF4E-3 enters large particles that increase in size during nutritional stress, LeishIF4G-4 is found only in the top fractions. Confocal microscopy localized LeishIF4E-3 (but not LeishIF4G-4) within nutritional stress-induced granules. Accordingly, interaction between the two proteins reduced upon starvation. We therefore propose that under normal conditions, LeishIF4G-4 sequesters LeishIF4E-3 in the cytoplasm. During a nutritional stress, LeishIF4E-3 is modified and released from LeishIF4G-4 to enter stress granules, where inactive mRNAs are stored. Binding of LeishIF4G-4 to LeishIF4E-3 requires a short peptide within the LeishIF4G-4 N-terminus, which bears no similarity to the consensus 4E-binding peptide, YXXXXLφ. Mutational analysis combined with structure prediction indicates that this interaction is based on an obligatory, conserved á helix in LeishIF4G-4. These features further highlight the uniqueness of LeishIF4E-3 and how it interacts with its binding partners.
Original language | English |
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Pages (from-to) | 1450-1460 |
Number of pages | 11 |
Journal | RNA Biology |
Volume | 9 |
Issue number | 12 |
DOIs | |
State | Published - 1 Jan 2012 |
Keywords
- 4E-binding peptide
- Leishmania
- RNA granules
- eIF4E
- eIF4G
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology