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Translational control by lysine-encoding A-rich sequences.

Arthur, Laura and Pavlovic-Djuranovic, Slavica and Smith-Koutmou, Kristin and Green, Rachel and Szczesny, Pawel and Djuranovic, Sergej (2015) Translational control by lysine-encoding A-rich sequences. Science advances, 1 (6). ISSN 2375-2548



Regulation of gene expression involves a wide array of cellular mechanisms that control the abundance of the RNA or protein products of that gene. Here we describe a gene-regulatory mechanism that is based on poly(A) tracks that stall the translation apparatus. We show that creating longer or shorter runs of adenosine nucleotides, without changes in the amino acid sequence, alters the protein output and the stability of mRNA. Sometimes these changes result in the production of an alternative "frame-shifted" protein product. These observations are corroborated using reporter constructs and in the context of recombinant gene sequences. Approximately two percent of genes in the human genome may be subject to this uncharacterized, yet fundamental form of gene regulation. The potential pool of regulated genes encodes many proteins involved in nucleic acid binding. We hypothesize that the genes we identify are part of a large network whose expression is fine-tuned by poly(A)-tracks, and we provide a mechanism through which synonymous mutations may influence gene expression in pathological states.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Bioinformatics
ID Code:1065
Deposited By: Pawel Szczesny
Deposited On:10 Dec 2015 09:47
Last Modified:10 Dec 2015 09:47

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