Modeling of mRNA deadenylation rates reveal a complex relationship between mRNA deadenylation and decay

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Agnieszka Czarnocka-Cieciura1,#, Jarosław Poznański2,#, Matti Turtola3, Rafał Tomecki2,4, Paweł S. Krawczyk1, Seweryn Mroczek4,1, Wiktoria Orzeł1, Upasana Saha5, Torben Heick Jensen5, Andrzej Dziembowski1,4*, Agnieszka Tudek2,* 1 International Institute of Molecular and Cell Biology, Księcia Trojdena 4, 02-109 Warsaw, Poland 2 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, 02-106 Warsaw, Poland 3 Department of Life Technologies, University of Turku, Biocity, Tykistökatu 6, 205240 Turku, Finland 4 University of Warsaw, Faculty of Biology, Miecznikowa 1, 02-089 Warsaw, Poland 5 Aarhus University, Department of Molecular Biology and Genetics – Universitetsbyen 81, 8000 Aarhus, Denmark # those authors contributed equally * correspondence should be addressed to: atudek@ibb.waw.pl or adziembowski@iimcb.gov.pl ABSTRACT Complete cytoplasmic polyadenosine tail (polyA-tail) deadenylation is thought to be essential for initiating mRNA decapping and subsequent degradation. To investigate this prevalent model, we conducted direct RNA sequencing of S. cerevisiae mRNAs derived from chase experiments under steady-state and stress condition. Subsequently, we developed a numerical model based on a modified gamma distribution function, which estimated the transcriptomic deadenylation rate at 10 A/min. A simplified independent method, based on the delineation of quantile polyA-tail values, showed a correlation between the decay and deadenylation rates of individual mRNAs, which appeared consistent within functional transcript groups and associated with codon optimality. Notably, these rates varied during the stress response. Detailed analysis of ribosomal protein-coding mRNAs (RPG mRNAs), constituting 40% of the transcriptome, singled out this transcript group. While deadenylation and decay of RPG mRNAs accelerated under heat stress, their degradation could proceed even when deadenylation was blocked, depending entirely on ongoing nuclear export. Our findings support the general primary function of deadenylation in dictating the onset of decapping, while also demonstrating complex relations between these processes.

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This research was performed thanks to the IIMCB IN-MOL-CELL Infrastructure funded by the European Union, co-financed under the European Funds for Smart Economy 2021-2027 (FENG) and theEuropean Union— NextGenerationEU.

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