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Tissue‐specific mechanisms of alternative polyadenylation: testis, brain, and beyond

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Abstract Changing the position of the poly(A) tail in an mRNA—alternative polyadenylation—is an important mechanism to increase the diversity of gene expression, especially in metazoans. Alternative polyadenylation often occurs in a tissue‐ or developmental stage‐specific manner and can significantly affect gene activity by changing the protein product generated, the stability of the transcript, its localization, or its translatability. Despite the important regulatory effects that alternative polyadenylation have on gene expression, only a sparse few examples have been mechanistically characterized. Here, we review the known mechanisms for the control of alternative polyadenylation, catalog the tissues that demonstrate a propensity for alternative polyadenylation, and focus on the proteins that are known to regulate alternative polyadenylation in specific tissues. We conclude that the field of alternative polyadenylation remains in its infancy, with possibilities for future investigation on the horizon. Given the profound effect alternative polyadenylation can have on gene expression and human health, improved understanding of alternative polyadenylation could lead to numerous advances in control of gene activity. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Development

Core and auxiliary proteins involved in tissue‐specific alternative polyadenylation. The pre‐mRNA (black line) consists of upstream sequence elements (UGUAN), the polyadenylation signal (AAUAAA), a cleavage site (arrow), the downstream sequence element (UUUUU), and the downstream G‐rich element (GGGGG). The core polyadenylation proteins consist of the cleavage and polyadenylation specificity factor proteins, the cleavage stimulation factor proteins, and mammalian cleavage factor I. Auxiliary (U2AF, hnRNP F, hnRNP H, and hnRNP I) and tissue‐specific (Nova‐1, βCstF‐64, τCstF‐64, ELL2, sex‐lethal, FPA, FY, and FCA) proteins are indicated.

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Proteins involved in testis and brain alternative polyadenylation. (a) Three forms of CstF‐64 are involved in polyadenylation. βCstF‐64 (middle) is an alternatively spliced variant of CstF‐64 (top) that is expressed in vertebrate neurons. τCstF‐64 (bottom) is an autosomal paralog of CstF‐64 that is expressed primarily in male germ cells in mammals. The RNA‐binding domain, CstF‐77 interaction domain (Hinge), proline‐ and glycine‐rich domain (Pro/Gly), MEARA amino acid repeats, and C‐terminal domain are indicated. (b) Expression patterns of alternative polyadenylation proteins during spermatogenesis. A timeline of spermatogenesis in mice has been shown (∼34 days). Cells that undergo mitotic division (spermatogonia), meiosis (spermatocytes), and postmeiotic development (round or elongating spermatids, and spermatozoa) are indicated. Expression periods for CstF‐64, τCstF‐64, CPSF‐160, CFIm25, CFIm68, and WDC146 are at bottom. XY inactivation indicates the period of male sex chromosome inactivation.

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RNA in Disease and Development > RNA in Development
RNA Processing > 3′ End Processing

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