Ending the Message Is Not So Simple

It is becoming increasingly apparent that there is a significant degree of regulated gene expression at the 3′ ends of mRNA. As well as the examples discussed above, a considerable number of genes use alternate poly(A) signals in the 3′ untranslated regions of their mRNAs. This may result in a further level of regulation, as although the same protein product will be produced, different 3′ UTRs will be formed which may alter the stability, translation, or transport of the mRNA. Possibly the limited examples of this type of gene regulation to come to light so far reflect more our lack of knowledge of the complete picture of gene regulation than the absence of true examples. Indeed the tendency of molecular geneticists to define mRNA 3′ ends only by cDNA cloning or RT-PCR means that very often the full complexity of alternative polyadenylation will be lost until more complete sequence data become available.

[1]  G. Caponigro,et al.  Multiple functions for the poly(A)-binding protein in mRNA decapping and deadenylation in yeast. , 1995, Genes & development.

[2]  G. Edwalds-Gilbert,et al.  Regulation of poly(A) site use during mouse B-cell development involves a change in the binding of a general polyadenylation factor in a B-cell stage-specific manner , 1995, Molecular and cellular biology.

[3]  J. Manley,et al.  The Polyadenylation Factor CstF-64 Regulates Alternative Processing of IgM Heavy Chain Pre-mRNA during B Cell Differentiation , 1996, Cell.

[4]  W. Boelens,et al.  The human U1A snRNP protein regulates polyadenylation via a direct interaction with poly(A) polymerase , 1994, Cell.

[5]  M. L. Peterson,et al.  The regulated production of mu m and mu s mRNA is dependent on the relative efficiencies of mu s poly(A) site usage and the c mu 4-to-M1 splice , 1989, Molecular and cellular biology.

[6]  J. Nevins,et al.  Identification of an activity in B-cell extracts that selectively impairs the formation of an immunoglobulin mu s poly(A) site processing complex , 1995, Molecular and cellular biology.

[7]  J. Steitz,et al.  Association with terminal exons in pre-mRNAs: a new role for the U1 snRNP? , 1993, Genes & development.

[8]  K. Murthy,et al.  Interaction between the U1 snRNP-A protein and the 160-kD subunit of cleavage-polyadenylation specificity factor increases polyadenylation efficiency in vitro. , 1996, Genes & development.

[9]  C. Baker,et al.  Sequences homologous to 5' splice sites are required for the inhibitory activity of papillomavirus late 3' untranslated regions , 1994, Molecular and cellular biology.

[10]  N. Proudfoot,et al.  Poly(A) site selection in the HIV-1 provirus: inhibition of promoter-proximal polyadenylation by the downstream major splice donor site. , 1995, Genes & development.

[11]  H. Lou,et al.  An intron enhancer recognized by splicing factors activates polyadenylation. , 1996, Genes & development.

[12]  M. Peterson.  Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: non-Ig RNA can be alternatively processed in B cells and plasma cells , 1994, Molecular and cellular biology.

[13]  A. Sachs,et al.  A common function for mRNA 5' and 3' ends in translation initiation in yeast. , 1995, Genes & development.

[14]  J. Nevins,et al.  Alternative poly(A) site utilization during adenovirus infection coincides with a decrease in the activity of a poly(A) site processing factor , 1993, Molecular and cellular biology.