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Alternative mRNA polyadenylation in eukaryotes: an effective regulator of gene expression

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Abstract Alternative RNA processing mechanisms, including alternative splicing and alternative polyadenylation, are increasingly recognized as important regulators of gene expression. This article will focus on what has recently been described about alternative polyadenylation in development, differentiation, and disease in higher eukaryotes. We will also describe how the evolving global methodologies for examining the cellular transcriptome, both experimental and bioinformatic, are revealing new details about the complex nature of alternative 3′ end formation as well as interactions with other RNA‐mediated and RNA processing mechanisms. WIREs RNA 2011 2 22–31 DOI: 10.1002/wrna.47 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Processing > 3' End Processing

Schematic of polyadenylation events. Light blue boxes, untranslated regions; darker blue boxes, coding regions; lines, introns. Messenger RNAs (mRNAs) with type I polyadenylation only have one polyadenylation signal in the 3 most exon. mRNAs with type II polyadenylation have more than one polyadenylation signal in the 3 most exon. Type III polyadenylation is alternative splicing coupled with alternative polyadenylation; type IIIi signals have one or more polyadenylation signals in upstream introns; type IIIe signals have one or more polyadenylation signals in upstream exons.

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Alternative polyadenylation of messenger RNA, as shown in the center of the figure, can affect many other cellular or organismal events. See text for details.

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Many RNA cis‐acting elements present in the 3 UTR can affect polyadenylation as well as other RNA processing or RNA‐mediated events, and these effects are intertwined. Regulation of gene expression by the 3 UTR depends on the presence of the cis‐acting regulatory element and may influence nuclear and cytoplasmic polyadenylation (pA signal and cytoplamic polyadenylation element—CPE), the stability of the messenger RNA (mRNA) produced (for example by AU elements), the subcellular localization of the mRNA, and translation or mRNA decay. Additionally, the presence of microRNA target sites in the 3 UTR may influence gene expression. The presence of the trans‐acting factors that bind to these elements or the microRNA that target the mRNA in the cell or tissue, at a particular stage and at the correct concentration, is essential for regulation to occur. Alternative polyadenylation in the 3 UTR generates different mRNA isoforms containing different cis‐acting elements.

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RNA Processing > 3′ End Processing
RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition

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