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Globin gene transcripts can utilize histone gene 3' end processing signals.

E Whitelaw, A Coates, N J Proudfoot

    Nucleic Acids Research
    |September 11, 1986
    PubMed
    Summary
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    Replacing the poly(A) site in alpha globin genes with histone signals stabilizes mRNA. Histone signals function independently but are less efficient than alpha globin poly(A) sites when competing.

    Area of Science:

    • Molecular Biology
    • Gene Regulation
    • mRNA Stability

    Background:

    • The polyadenylation (poly(A)) site is crucial for mRNA stability and processing.
    • Deletion of the poly(A) site in the human alpha globin gene leads to unstable mRNA and reduced gene function.

    Purpose of the Study:

    • To investigate the role of alternative 3' end processing signals in stabilizing alpha globin mRNA.
    • To determine if mouse histone H4 3' end processing signals can confer stability to alpha globin transcripts.

    Main Methods:

    • Gene engineering to delete the alpha globin poly(A) site and replace it with mouse histone H4 3' end processing signals.
    • Analysis of hybrid alpha/H4 mRNA levels, localization (cytoplasmic), and polyadenylation status.
    • Comparative analysis of signal utilization when alpha globin and histone signals are placed in tandem.

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    Main Results:

    • Replacing the alpha globin poly(A) site with histone H4 3' end processing signals yielded stable, cytoplasmic, and poly(A)- hybrid mRNA.
    • Histone 3' end processing signals function independently of their native promoter.
    • In a competitive scenario, alpha globin poly(A) site signals were exclusively utilized over histone signals, indicating lower efficiency of the latter.

    Conclusions:

    • Mouse histone 3' end processing signals can stabilize normally polyadenylated transcripts (alpha globin) by providing a poly(A)- terminus.
    • Histone 3' end processing signals are functional in a heterologous gene context.
    • The alpha globin poly(A) site is more efficient than histone 3' end processing signals when both are present and competing.