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Related Concept Videos

Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Measurement of mRNA Decay Rates in Saccharomyces cerevisiae Using rpb1-1 Strains
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Neighboring codon adjacent nucleotides have a conserved influence on mRNA decay.

Reed S Sorenson, Leslie E Sieburth

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    mRNA stability in plants is influenced by codon optimality, similar to yeast. Codon context, not just tRNA levels, also impacts mRNA decay rates, revealing a new selection mechanism.

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    Area of Science:

    • Molecular Biology
    • Genetics
    • Plant Science

    Background:

    • Genetic code degeneracy impacts mRNA stability in yeast.
    • Codon optimality, defined by tRNA supply and demand, affects mRNA decay rates.
    • The role of this mechanism in plants and other factors influencing codon optimality were unexplored.

    Purpose of the Study:

    • To investigate whether codon optimality influences mRNA decay rates in plants.
    • To explore factors beyond charged tRNA abundance that affect codon optimality.
    • To determine the extent to which codon usage impacts mRNA stability in Arabidopsis.

    Main Methods:

    • Correlating biased codon usage with mRNA decay rates in Arabidopsis.
    • Testing a codon-optimality model using synonymously recoded genes.
    • Analyzing mRNA decay rates in transgenic plants and comparing with model predictions.
    • Investigating the influence of codon context on mRNA decay.

    Main Results:

    • Biased codon usage in Arabidopsis correlated with mRNA decay rates.
    • A codon-optimality model accurately predicted mRNA decay rates for recoded genes.
    • The NOT3 gene's conserved sensor domain suggests a conserved mechanism for sensing suboptimal codons.
    • Codon context, specifically adjacent nucleotides, influenced mRNA decay rates independently of tRNA levels.

    Conclusions:

    • Codon frequencies explain 21% of mRNA decay rate variance in plants.
    • Codon optimality-mediated decay is one of several mechanisms regulating plant mRNA stability.
    • Codon context is an additional factor affecting mRNA stability.
    • A paradigm of selection among synonymous codons decoded via wobble base pairing is established.