In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs

RNA
Stanislava GunišováLeoš Shivaya Valášek

Abstract

Translational control in eukaryotes is exerted by many means, one of which involves a ribosome translating multiple cistrons per mRNA as in bacteria. It is called reinitiation (REI) and occurs on mRNAs where the main ORF is preceded by a short upstream uORF(s). Some uORFs support efficient REI on downstream cistrons, whereas some others do not. The mRNA of yeast transcriptional activator GCN4 contains four uORFs of both types that together compose an intriguing regulatory mechanism of its expression responding to nutrients' availability and various stresses. Here we subjected all GCN4 uORFs to a comprehensive analysis to identify all REI-promoting and inhibiting cis-determinants that contribute either autonomously or in synergy to the overall efficiency of REI on GCN4. We found that the 3' sequences of uORFs 1-3 contain a conserved AU1-2A/UUAU2 motif that promotes REI in position-specific, autonomous fashion such as the REI-promoting elements occurring in 5' sequences of uORF1 and uORF2. We also identified autonomous and transferable REI-inhibiting elements in the 3' sequences of uORF2 and uORF3, immediately following their AU-rich motif. Furthermore, we analyzed contributions of coding triplets and terminating stop codon tetra...Continue Reading

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Citations

Oct 30, 2016·RNA Biology·Luis Enrique Cabrera-QuioAndrea Pauli
Jul 27, 2017·RNA Biology·Vladislava HronováLeoš Shivaya Valášek
Oct 6, 2017·Nucleic Acids Research·Leoš Shivaya ValášekStanislava Gunišová
Apr 7, 2018·Wiley Interdisciplinary Reviews. RNA·Nikolay E Shirokikh, Thomas Preiss
Dec 28, 2017·FEMS Microbiology Reviews·Stanislava GunišováLeoš Shivaya Valášek
Jul 19, 2018·Yeast·Robert A Crawford, Graham D Pavitt
Nov 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Meredith CorleyAlain Laederach
Aug 9, 2019·Nucleic Acids Research·Yizhu LinC Joel McManus
Aug 23, 2019·International Journal of Molecular Sciences·Yoshika JanapalaNikolay E Shirokikh
Aug 2, 2017·Annual Review of Cell and Developmental Biology·Serge PlazaFrançois Payre
Oct 24, 2019·Nucleic Acids Research·Kristýna PoncováLeoš Shivaya Valášek
Aug 6, 2021·Nucleic Acids Research·Mahabub Pasha MohammadLeoš Shivaya Valášek

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