Journal of theoretical biologyOct 18, 2000

How cells check and start protein-making depending on mRNA start signals and tail

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

Two kinetic proofreading scanning models describe the translation initiation dependency on the 5' cap and 3' poly(A) tail in eukaryotic mRNA.

Model I involves the initiation factor complex scanning from the 5' end of mRNA, while Model II allows scanning from any site in the 5' untranslated region (UTR).
Both models indicate that the translation of mRNAs with structured 5' UTRs relies heavily on the presence of a 5' cap and poly(A) tail.
In contrast, mRNAs with unstructured 5' UTRs show reduced dependency on these features for translation.
The models explain various phenomena, including the effects of exogenous poly(A) on translation and the repression of host mRNA during adenovirus and Vaccinia virus infections.
They also account for the heat shock response, where normal mRNA translation is repressed while hsp mRNA translation is stimulated.
The synergistic effect of the cap and poly(A) tail in enhancing translation is highlighted within these models.

Simplified

Two simplified 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 different 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 effect 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 effect of cap and poly(A) tail on stimulating translation. The kinetic proofreading scanning models provide a coherent interpretation of those phenomena.

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How cells check and start protein-making depending on mRNA start signals and tail

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