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Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor ?.

ABSTRACT: mRNAs encodes not only information that determines amino acid sequences but also additional layers of information that regulate the translational processes. Notably, translational halt at specific position caused by rare codons or stable RNA structures is one of the potential factors regulating the protein expressions and structures. In this study, a quadruplex-forming potential (QFP) sequence derived from an open reading frame of human estrogen receptor ? (hER?) mRNA was revealed to form parallel G-quadruplex and halt the translation elongation in vitro. Moreover, when the full-length hER? and variants containing synonymous mutations in the QFP sequence were expressed in cells, translation products cleaved at specific site were observed in quantities dependent on the thermodynamic stability of the G-quadruplexes. These results suggest that the G-quadruplex formation in the coding region of the hER? mRNA impacts folding and proteolysis of hER? protein by slowing down or temporarily stalling the translation elongation.

SUBMITTER: Endoh T

PROVIDER: S-EPMC3695533 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor α.

Endoh Tamaki T Kawasaki Yu Y Sugimoto Naoki N

Nucleic acids research 20130424 12

mRNAs encodes not only information that determines amino acid sequences but also additional layers of information that regulate the translational processes. Notably, translational halt at specific position caused by rare codons or stable RNA structures is one of the potential factors regulating the protein expressions and structures. In this study, a quadruplex-forming potential (QFP) sequence derived from an open reading frame of human estrogen receptor α (hERα) mRNA was revealed to form parall ...[more]

PMID: 23620292

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Project description:Translation of an mRNA in eukaryotes starts at AUG in most cases. Near-cognate codons (NCCs) such as UUG, ACG and AUU are also used as start sites at low levels in S. cerevisiae. Initiation from NCCs or AUGs in the 5’-untranslated regions (UTRs) of mRNAs can lead to translation of upstream open reading frames (uORFs) that might regulate expression of the main ORF (mORF). Although there is some circumstantial evidence that the translation of uORFs can be affected by environmental conditions, little is known about how it is affected by changes in growth temperature. Using reporter assays, we found that changes in growth temperature can affect translation from NCC start sites in yeast cells, suggesting the possibility that gene expression could be regulated by temperature by altering use of different uORF start codons. Using ribosome profiling, we provide evidence that growth temperature regulates the efficiency of translation of nearly 200 uORFs in S. cerevisiae. Of these uORFs, most that start with an AUG codon have increased translational efficiency at 37 ˚C relative to 30 ˚C and decreased efficiency at 20 ˚C. For translationally regulated uORFs starting with NCCs, we did not observe a general trend for the direction of regulation as a function of temperature, suggesting mRNA-specific features can determine the mode of temperature-dependent regulation. Consistent with this conclusion, the position of the uORFs in the 5’-leader relative to the 5’-cap and the start codon of the main ORF correlates with the direction of temperature-dependent regulation of uORF translation. We have identified several novel cases in which changes in uORF translation are inversely correlated with changes in the translational efficiency of the downstream main ORF. Our data suggest that translation of these mRNAs is subject to temperature-dependent, uORF-mediated regulation. Overall, our data suggest that alterations in the translation of specific uORFs by temperature can regulate gene expression in S. cerevisiae.

Dataset Information

Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor ?.

Publications

Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor α.

Similar Datasets

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