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PMID: 21956945 Published · ppublish English Journal Article Review

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

Wiley interdisciplinary reviews. RNA ·Vol. 1 ·No. 3 ·2010-00-00 ·Pages 494-501

MacDonald CC, McMahon KW

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.

MeSH Terms
Alternative Splicing/genetics,physiology Animals Brain/metabolism,physiology Humans Male Models, Biological Organ Specificity/genetics Polyadenylation/genetics,physiology Spermatogenesis/genetics,physiology Testis/metabolism
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
MacDonald Clinton C
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6540, USA. clint.macdonald@ttuhsc.edu
McMahon K Wyatt
References (46)
46 references, click to expand
  1. Post-transcriptional control in the male germ line.
    Reprod Biomed Online. 2005 Jan;10(1):55-63 PMID: 15705295
  2. HITS-CLIP yields genome-wide insights into brain alternative RNA processing.
    Nature. 2008 Nov 27;456(7221):464-9 PMID: 18978773
  3. Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline.
    EMBO J. 2006 Mar 22;25(6):1263-72 PMID: 16511567
  4. RNA truncation by premature polyadenylation attenuates human mobile element activity.
    Nat Genet. 2003 Dec;35(4):363-6 PMID: 14625551
  5. 3' end mRNA processing: molecular mechanisms and implications for health and disease.
    EMBO J. 2008 Feb 6;27(3):482-98 PMID: 18256699
  6. Role for Fox-1/Fox-2 in mediating the neuronal pathway of calcitonin/calcitonin gene-related peptide alternative RNA processing.
    Mol Cell Biol. 2007 Feb;27(3):830-41 PMID: 17101796
  7. The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice.
    J Biol Chem. 2001 Mar 16;276(11):8044-50 PMID: 11113135
  8. Role of plant RNA-binding proteins in development, stress response and genome organization.
    Trends Plant Sci. 2009 Apr;14(4):229-36 PMID: 19285908
  9. Biased chromatin signatures around polyadenylation sites and exons.
    Mol Cell. 2009 Oct 23;36(2):245-54 PMID: 19854133
  10. The Drosophila homologue of the 64 kDa subunit of cleavage stimulation factor interacts with the 77 kDa subunit encoded by the suppressor of forked gene.
    Nucleic Acids Res. 2000 Jan 15;28(2):520-6 PMID: 10606651
  11. CLIP identifies Nova-regulated RNA networks in the brain.
    Science. 2003 Nov 14;302(5648):1212-5 PMID: 14615540
  12. Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites.
    Mol Cell Biol. 1984 Oct;4(10):2151-60 PMID: 6334229
  13. Targeted 3' processing of antisense transcripts triggers Arabidopsis FLC chromatin silencing.
    Science. 2010 Jan 1;327(5961):94-7 PMID: 19965720
  14. Progressive lengthening of 3' untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development.
    Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7028-33 PMID: 19372383
  15. Elevated levels of the polyadenylation factor CstF 64 enhance formation of the 1kB Testis brain RNA-binding protein (TB-RBP) mRNA in male germ cells.
    Mol Reprod Dev. 2001 Apr;58(4):460-9 PMID: 11241784
  16. A core complex of CPSF73, CPSF100, and Symplekin may form two different cleavage factors for processing of poly(A) and histone mRNAs.
    Mol Cell. 2009 May 15;34(3):322-32 PMID: 19450530
  17. The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation.
    Cell. 1996 Nov 29;87(5):941-52 PMID: 8945520
  18. Biased alternative polyadenylation in human tissues.
    Genome Biol. 2005;6(12):R100 PMID: 16356263
  19. X chromosomes, retrogenes and their role in male reproduction.
    Trends Endocrinol Metab. 2004 Mar;15(2):79-83 PMID: 15036254
  20. Interallelic complementation at the suppressor of forked locus of Drosophila reveals complementation between suppressor of forked proteins mutated in different regions.
    Genetics. 1996 Apr;142(4):1225-35 PMID: 8846900
  21. Alternative isoform regulation in human tissue transcriptomes.
    Nature. 2008 Nov 27;456(7221):470-6 PMID: 18978772
  22. Pre-messenger RNA cleavage factor I (CFIm): potential role in alternative polyadenylation during spermatogenesis.
    Biol Reprod. 2008 Mar;78(3):472-82 PMID: 18032416
  23. Protein factors in pre-mRNA 3'-end processing.
    Cell Mol Life Sci. 2008 Apr;65(7-8):1099-122 PMID: 18158581
  24. A developmental switch in transcription factor isoforms during spermatogenesis controlled by alternative messenger RNA 3'-end formation.
    Biol Reprod. 2006 Sep;75(3):318-23 PMID: 16723505
  25. Systematic variation in mRNA 3'-processing signals during mouse spermatogenesis.
    Nucleic Acids Res. 2007;35(1):234-46 PMID: 17158511
  26. Loss of polyadenylation protein tauCstF-64 causes spermatogenic defects and male infertility.
    Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20374-9 PMID: 18077340
  27. Differences in polyadenylation site choice between somatic and male germ cells.
    BMC Mol Biol. 2006 Oct 12;7:35 PMID: 17038175
  28. Arabidopsis CLP1-SIMILAR PROTEIN3, an ortholog of human polyadenylation factor CLP1, functions in gametophyte, embryo, and postembryonic development.
    Plant Physiol. 2008 Dec;148(4):2059-69 PMID: 18971429
  29. Arabidopsis PCFS4, a homologue of yeast polyadenylation factor Pcf11p, regulates FCA alternative processing and promotes flowering time.
    Plant J. 2008 Jun;54(5):899-910 PMID: 18298670
  30. Role of RNA-binding proteins in mammalian spermatogenesis.
    Int J Androl. 2010 Feb;33(1):2-12 PMID: 19281489
  31. A large-scale analysis of mRNA polyadenylation of human and mouse genes.
    Nucleic Acids Res. 2005 Jan 12;33(1):201-12 PMID: 15647503
  32. The spen family protein FPA controls alternative cleavage and polyadenylation of RNA.
    Dev Cell. 2010 Feb 16;18(2):203-13 PMID: 20079695
  33. Molecular mechanisms of eukaryotic pre-mRNA 3' end processing regulation.
    Nucleic Acids Res. 2010 May;38(9):2757-74 PMID: 20044349
  34. FY is an RNA 3' end-processing factor that interacts with FCA to control the Arabidopsis floral transition.
    Cell. 2003 Jun 13;113(6):777-87 PMID: 12809608
  35. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.
    Cell. 2009 Aug 21;138(4):673-84 PMID: 19703394
  36. Molecular architecture of the human pre-mRNA 3' processing complex.
    Mol Cell. 2009 Feb 13;33(3):365-76 PMID: 19217410
  37. Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling.
    BMC Genomics. 2008 May 14;9:220 PMID: 18479511
  38. Overexpression of the CstF-64 and CPSF-160 polyadenylation protein messenger RNAs in mouse male germ cells.
    Biol Reprod. 2001 Jun;64(6):1722-9 PMID: 11369601
  39. Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing.
    Nat Immunol. 2009 Oct;10(10):1102-9 PMID: 19749764
  40. Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3'-UTRs.
    Nucleic Acids Res. 2006;34(21):6264-71 PMID: 17098938
  41. An intronic polyadenylation site in human and mouse CstF-77 genes suggests an evolutionarily conserved regulatory mechanism.
    Gene. 2006 Feb 1;366(2):325-34 PMID: 16316725
  42. Two distinct forms of the 64,000 Mr protein of the cleavage stimulation factor are expressed in mouse male germ cells.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6763-8 PMID: 10359786
  43. Developmental distribution of the polyadenylation protein CstF-64 and the variant tauCstF-64 in mouse and rat testis.
    Biol Reprod. 2004 Apr;70(4):1080-7 PMID: 14681198
  44. A family of splice variants of CstF-64 expressed in vertebrate nervous systems.
    BMC Mol Biol. 2009 Mar 12;10:22 PMID: 19284619
  45. A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner.
    Biochem Biophys Res Commun. 2001 Jan 26;280(3):656-63 PMID: 11162572
  46. Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition.
    Genes Dev. 2005 Jun 1;19(11):1315-27 PMID: 15937220
Article Info
Journal
Wiley interdisciplinary reviews. RNA
Abbr.
Wiley Interdiscip Rev RNA
ISSN
1757-7012
Published
2010-00-00
Pages
494-501
Language
English
Region
United States
NLM ID
101536955
PMCID
PMC5417544
Subset
IM
Grants
NICHD NIH HHS · R01 HD037109 · United States
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