Kinetic Proofreading Scanning Models for Eukaryotic Translational Initiation: the Cap and Poly(A) Tail Dependency of Translation

✍ Scribed by XIPING BI; DIXIE J. GOSS

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 222 KB
• Volume: 207
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.2000.2163

✦ Synopsis

Two simpli"ed kinetic proofreading scanning (KPS) models were proposed to describe the 5 cap and 3 poly(A) tail dependency of eukaryotic translation initiation. In Model I, the initiation factor complex starts scanning and unwinding the secondary structure of the 5 untranslated region (UTR) from the 5 terminus of mRNA. In Model II, the initiation factor complex starts scanning from any binding site in the 5 UTR. In both models, following ATP hydrolysis, the initiation factor complex either dissociates from mRNA or continues to scan and unwind RNA secondary structure in the 5 UTR. This step repeats n times until the AUG codon is reached. These two models show very di!erent cap and/or poly(A) tail dependency of translation initiation. The models predict that both cap and poly(A) tail dependencies of translation, and translatability of mRNAs are coupled with the structure of 5 UTR: the translation of mRNA with structured 5 UTR is strongly cap-and poly(A) tail-dependent; while translation of mRNA with unstructured 5 UTR is less cap-and poly(A) tail-dependent. We use these two models to explain: (1) the cap and poly(A) tail dependence of translation; (2) the e!ect of exogenous poly(A) on translation; (3) repression of host mRNA and translation of late adenovirus mRNA in the late phase of adenovirus infection; (4) repression of host mRNA and translation of Vaccinia virus mRNA in virus-infected cell; (5) heat shock repression of translation of normal mRNA and stimulation of translation of hsp mRNA; and (6) the synergistic e!ect of cap and poly(A) tail on stimulating translation. The kinetic proofreading scanning models provide a coherent interpretation of those phenomena.