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.