Table 1.
Eukaryotic initiation factors
| Name | Subunits Mol. wt. (kDa) | Function |
|---|---|---|
| Core Initiation Factors | ||
| eIF2 | 3 (36.1, 38.4, 51.1) | Forms an eIF2/GTP/Met-tRNAi ternary complex that binds to the 40S subunit, thus mediating ribosomal recruitment of Met-tRNAi |
| eIF3 | 13 (800 total) | Binds 40S subunits, eIFs 1, 4G, 5; stimulates binding of eIF2/GTP/Met-tRNAi to 40S subunits; promotes attachment of 43S complexes to mRNA and subsequent scanning; possesses ribosome dissociation and anti-association activities preventing joining of 40S and 60S subunits |
| eIF1 | 1 (12.7) | Ensures the fidelity of initiation codon selection; promotes ribosomal scanning; stimulates binding of eIF2/GTP/Met-tRNAi to 40S subunits; prevents premature eIF5-induced hydrolysis of eIF2-bound GTP and Pi release |
| eIF1A | 1 (16.5) | Stimulates binding of eIF2/GTP/Met-tRNAi to 40S subunits; cooperates with eIF1 in promoting ribosomal scanning and initiation codon selection |
| eIF4E | 1 (24.5) | Binds to the m7GpppG 5’-terminal ‘cap’ structure of mRNA |
| eIF4A* | 1 (46.1) | DEAD-box ATPase and ATP-dependent RNA helicase |
| eIF4G** | 1 (175.5) | Binds eIF4E, eIF4A, eIF3, PABP, SLIP1 and mRNA (Fig. 3A); enhances eIF4A’s helicase activity |
| eIF4F | 3 (246.1 total) | Cap-binding complex, comprising eIF4E, eIF4A and eIF4G; unwinds 5’-proximal region of mRNA and mediates attachment to it of 43S complexes; assist ribosomal complexes during scanning |
| eIF4B | 1 (69.3) | RNA-binding protein; enhances eIF4A’s helicase activity |
| eIF4H | 1 (27.4) | RNA-binding protein; enhances eIF4A’s helicase activity; homologous to a fragment of eIF4B |
| eIF5 | 1 (49.2) | GTPase-activating protein specific for eIF2•GTP that induces hydrolysis of eIF2-bound GTP upon recognition of the initiation codon |
| eIF5B | 1 (138.9) | Ribosome-dependent GTPase; mediates ribosomal subunit joining |
| eIF2B | 5 (33.7, 39.0, 50.2, 59.7, 80.3) | Guanosine nucleoside exchange factor that promotes GDP/GTP exchange on eIF2 |
| Auxiliary factors | ||
| DHX29 | 1 (155.3) | A DExH-box-containing protein; binds 40S subunit; promotes ribosomal scanning on mRNAs with long, highly-structured 5’UTRs |
| Ded1p | 1 (65.6) | DEAD-box NTPase/RNA helicase; potentially promotes scanning in S. cerevisiae |
| eIF6 | 1 (26.6) | Binds 60S subunits; anti-association factor that prevents joining of 40S subunits to 60S subunits |
| p97 | 1 (102.4) | Closely related to the carboxy-terminal two-thirds of eIF4GI; binds eIF4A and eIF3; promotes initiation in a potentially mRNA-specific manner |
| PABP | 1 (70.7) | Binds to the mRNA 3’-poly(A) tail, eIF4G and eRF3; enhances binding of eIF4F to the cap; may facilitate recruitment of recycled post-termination 40S subunits back to the 5’-end of mRNA. |
*
Two paralogues (eIF4AI and eIF4AII), encoded by different genes, are functionally indistinguishable, but “eIF4AIII” has no activity as an eIF.
**
Two paralogues (eIF4GI and eIF4GII), encoded by different genes, are functionally similar but show some selectivity towards different mRNAs. eIF4GI is generally the more abundant.