Probabilistic models of uORF-mediated ATF4 translation control

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dc.contributor.authorMarasco, Olivia N. J. M.
dc.contributor.authorRoussel, Marc R.
dc.contributor.authorThakor, Nehal
dc.date.accessioned2022-01-13T23:29:15Z
dc.date.available2022-01-13T23:29:15Z
dc.date.issued2022
dc.descriptionAccepted author manuscript. en_US
dc.description.abstractATF4 is a key transcription factor that activates transcription of genes needed to respond to cellular stress. Although the mRNA encoding ATF4 is present at constant levels in the cell during the initial response, translation of ATF4 increases under conditions of cellular stress while the global translation rate decreases. We study two models for the control system that regulates the translation of ATF4, both based on the Vattem-Wek hypothesis. This hypothesis is based on a race to reload, following the translation of a small upstream open reading frame (uORF), the ternary complex that brings the initiator tRNA to the ribosome as the 40S subunit scans along the mRNA, encountering first a start codon for an inhibitory uORF whose reading frame overlaps the start of the ATF4 coding sequence. We develop a pair of simple, analytic, probabilistic models, one of which assumes all nucleotide triplets have identical kinetic properties, while the other recognizes the existence of triplets at which the ternary complex loads more efficiently. We also consider two different functions representing the dependence of the rate of initiation at uORF1 on the ternary complex concentration. In keeping with the theme of this Special Issue, we studied the properties of these models in a Maple document, which can easily be modified to consider different parameters, translation rate initiation functions, and so on.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationMarasco, O. N. J. M., Roussel, M. R., & Thakor, N. (2022). Probabilistic models of uORF-mediated ATF4 translation control. Mathematical Biosciences, 343. https://doi.org/10.1016/j.mbs.2021.108762en_US
dc.identifier.urihttps://hdl.handle.net/10133/6132
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.urlhttps://doi.org/10.1016/j.mbs.2021.108762en_US
dc.subjectTranslation controlen_US
dc.subjectATF4en_US
dc.subjectUpstream open reading frameen_US
dc.subjectProbabilistic modelen_US
dc.subjectComputer algebraen_US
dc.subjectDynamic publicationen_US
dc.titleProbabilistic models of uORF-mediated ATF4 translation controlen_US
dc.typeArticleen_US
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Roussel, Marc
Thakor, Nehalkumar