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PMID: 21278855 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

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

Wiley interdisciplinary reviews. RNA ·Vol. 2 ·No. 1 ·2011-00-00 ·Pages 23-31

Lutz CS, Moreira A

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.

MeSH Terms
Alternative Splicing/genetics,physiology Animals Efficiency Eukaryota/genetics,metabolism Eukaryotic Cells/metabolism Gene Expression Regulation Humans Models, Biological Polyadenylation/genetics,physiology RNA, Messenger/genetics,metabolism
Chemicals
RNA, Messenger
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lutz Carol S
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, MSB E671, 185 South Orange Ave., Newark, NJ 07103, USA. lutzcs@umdnj.edu
Moreira Alexandra
References (71)
71 references, click to expand
  1. A genomic analysis of RNA polymerase II modification and chromatin architecture related to 3' end RNA polyadenylation.
    Genome Res. 2008 Aug;18(8):1224-37 PMID: 18487515
  2. Alternative polyadenylation of MeCP2: Influence of cis-acting elements and trans-acting factors.
    RNA Biol. 2010 May-Jun;7(3):361-72 PMID: 20400852
  3. Mechanism and regulation of mRNA polyadenylation.
    Genes Dev. 1997 Nov 1;11(21):2755-66 PMID: 9353246
  4. Systematic variation in mRNA 3'-processing signals during mouse spermatogenesis.
    Nucleic Acids Res. 2007;35(1):234-46 PMID: 17158511
  5. Molecular mechanisms of eukaryotic pre-mRNA 3' end processing regulation.
    Nucleic Acids Res. 2010 May;38(9):2757-74 PMID: 20044349
  6. Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved.
    EMBO J. 1995 Aug 1;14(15):3809-19 PMID: 7641699
  7. Integrating mRNA processing with transcription.
    Cell. 2002 Feb 22;108(4):501-12 PMID: 11909521
  8. The 3' untranslated region of messenger RNA: A molecular 'hotspot' for pathology?
    Nat Med. 2000 Jun;6(6):637-41 PMID: 10835679
  9. 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
  10. Increased rate of RNA-polyadenylation. An early response in Concanavalin A activated lymphocytes.
    Exp Cell Res. 1978 Jan;111(1):175-84 PMID: 563795
  11. Biased chromatin signatures around polyadenylation sites and exons.
    Mol Cell. 2009 Oct 23;36(2):245-54 PMID: 19854133
  12. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation.
    Science. 2007 Mar 16;315(5818):1576-9 PMID: 17322030
  13. Combinatorial control of signal-induced exon repression by hnRNP L and PSF.
    Mol Cell Biol. 2007 Oct;27(19):6972-84 PMID: 17664280
  14. Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals.
    EMBO J. 2007 Jun 6;26(11):2658-69 PMID: 17464285
  15. Complex protein interactions within the human polyadenylation machinery identify a novel component.
    Mol Cell Biol. 2000 Mar;20(5):1515-25 PMID: 10669729
  16. HITS-CLIP yields genome-wide insights into brain alternative RNA processing.
    Nature. 2008 Nov 27;456(7221):464-9 PMID: 18978773
  17. Probe-level analysis of expression microarrays characterizes isoform-specific degradation during mouse oocyte maturation.
    PLoS One. 2009 Oct 16;4(10):e7479 PMID: 19834616
  18. 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
  19. Cracking the egg: molecular dynamics and evolutionary aspects of the transition from the fully grown oocyte to embryo.
    Genes Dev. 2006 Oct 1;20(19):2713-27 PMID: 17015433
  20. Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):405-45 PMID: 10357856
  21. Regulation of alternative polyadenylation by genomic imprinting.
    Genes Dev. 2008 May 1;22(9):1141-6 PMID: 18451104
  22. Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation.
    RNA. 2005 Oct;11(10):1485-93 PMID: 16131587
  23. An extensive network of coupling among gene expression machines.
    Nature. 2002 Apr 4;416(6880):499-506 PMID: 11932736
  24. Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes.
    Cancer Res. 2009 Dec 15;69(24):9422-30 PMID: 19934316
  25. Hu proteins regulate polyadenylation by blocking sites containing U-rich sequences.
    J Biol Chem. 2007 Jan 26;282(4):2203-10 PMID: 17127772
  26. polo encodes a protein kinase homolog required for mitosis in Drosophila.
    Genes Dev. 1991 Dec;5(12A):2153-65 PMID: 1660828
  27. Alternative polyadenylation: a mechanism maximizing transcriptome diversity in higher eukaryotes.
    Plant Signal Behav. 2009 May;4(5):440-2 PMID: 19816115
  28. 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
  29. ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA deadenylation/degradation system.
    Genes Dev. 1999 Jan 15;13(2):188-201 PMID: 9925643
  30. Upstream elements present in the 3'-untranslated region of collagen genes influence the processing efficiency of overlapping polyadenylation signals.
    J Biol Chem. 2002 Nov 8;277(45):42733-40 PMID: 12200454
  31. The highways and byways of mRNA decay.
    Nat Rev Mol Cell Biol. 2007 Feb;8(2):113-26 PMID: 17245413
  32. Enhancer of rudimentaryp1, e(r)p1, a highly conserved enhancer of the rudimentary gene.
    Genetics. 1994 Dec;138(4):1163-70 PMID: 7896098
  33. Autoregulation at the level of mRNA 3' end formation of the suppressor of forked gene of Drosophila melanogaster is conserved in Drosophila virilis.
    Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14302-7 PMID: 9826695
  34. Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells.
    Annu Rev Biochem. 1996;65:693-739 PMID: 8811193
  35. The upstream sequence element of the C2 complement poly(A) signal activates mRNA 3' end formation by two distinct mechanisms.
    Genes Dev. 1998 Aug 15;12(16):2522-34 PMID: 9716405
  36. Biased alternative polyadenylation in human tissues.
    Genome Biol. 2005;6(12):R100 PMID: 16356263
  37. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons.
    Science. 2002 Mar 22;295(5563):2258-61 PMID: 11910109
  38. Alternative poly(A) site selection in complex transcription units: means to an end?
    Nucleic Acids Res. 1997 Jul 1;25(13):2547-61 PMID: 9185563
  39. RNA processing and its regulation: global insights into biological networks.
    Nat Rev Genet. 2010 Jan;11(1):75-87 PMID: 20019688
  40. Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline.
    EMBO J. 2006 Mar 22;25(6):1263-72 PMID: 16511567
  41. Protein factors in pre-mRNA 3'-end processing.
    Cell Mol Life Sci. 2008 Apr;65(7-8):1099-122 PMID: 18158581
  42. hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells.
    Mol Cell Biol. 2001 Feb;21(4):1228-38 PMID: 11158309
  43. Homology with Saccharomyces cerevisiae RNA14 suggests that phenotypic suppression in Drosophila melanogaster by suppressor of forked occurs at the level of RNA stability.
    Genes Dev. 1993 Feb;7(2):241-9 PMID: 8436295
  44. Differential repression of alternative transcripts: a screen for miRNA targets.
    PLoS Comput Biol. 2006 May;2(5):e43 PMID: 16699595
  45. Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition.
    Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11095-100 PMID: 9736695
  46. Alternative polyadenylation: a twist on mRNA 3' end formation.
    ACS Chem Biol. 2008 Oct 17;3(10):609-17 PMID: 18817380
  47. Pre-mRNA processing reaches back to transcription and ahead to translation.
    Cell. 2009 Feb 20;136(4):688-700 PMID: 19239889
  48. Polypyrimidine tract binding protein modulates efficiency of polyadenylation.
    Mol Cell Biol. 2004 May;24(10):4174-83 PMID: 15121839
  49. The G-rich auxiliary downstream element has distinct sequence and position requirements and mediates efficient 3' end pre-mRNA processing through a trans-acting factor.
    Nucleic Acids Res. 1995 May 11;23(9):1625-31 PMID: 7784220
  50. A polyadenylation factor subunit is the human homologue of the Drosophila suppressor of forked protein.
    Nature. 1994 Dec 1;372(6505):471-4 PMID: 7984242
  51. Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival.
    Blood. 2007 Jun 1;109(11):4599-606 PMID: 17299095
  52. A large-scale analysis of mRNA polyadenylation of human and mouse genes.
    Nucleic Acids Res. 2005 Jan 12;33(1):201-12 PMID: 15647503
  53. Life and death in the cytoplasm: messages from the 3' end.
    Curr Opin Genet Dev. 1997 Apr;7(2):220-32 PMID: 9115434
  54. Terminal riboadenylate transferase in human lymphocytes.
    Nature. 1974 Mar 29;248(447):407-9 PMID: 4823664
  55. Reprogramming of 3' untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types.
    PLoS One. 2009 Dec 23;4(12):e8419 PMID: 20037631
  56. Direct interaction of the U1 snRNP-A protein with the upstream efficiency element of the SV40 late polyadenylation signal.
    Genes Dev. 1994 Mar 1;8(5):576-86 PMID: 7926751
  57. Specific trans-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3'-UTR.
    RNA. 2007 Jul;13(7):1103-15 PMID: 17507659
  58. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene.
    Genes Dev. 2007 May 1;21(9):1025-30 PMID: 17437991
  59. Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells.
    Immunity. 1999 Feb;10(2):261-9 PMID: 10072078
  60. An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data.
    PLoS Comput Biol. 2009 Dec;5(12):e1000598 PMID: 20011106
  61. 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
  62. Molecular architecture of the human pre-mRNA 3' processing complex.
    Mol Cell. 2009 Feb 13;33(3):365-76 PMID: 19217410
  63. Alternative polyadenylation variants of the RNA binding protein, HuR: abundance, role of AU-rich elements and auto-Regulation.
    Nucleic Acids Res. 2009 Jun;37(11):3612-24 PMID: 19359363
  64. A history of poly A sequences: from formation to factors to function.
    Prog Nucleic Acid Res Mol Biol. 2002;71:285-389 PMID: 12102557
  65. 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
  66. Tissue-specific autoregulation of Drosophila suppressor of forked by alternative poly(A) site utilization leads to accumulation of the suppressor of forked protein in mitotically active cells.
    RNA. 2000 Nov;6(11):1529-38 PMID: 11105753
  67. Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs.
    Nucleic Acids Res. 1998 Jun 15;26(12):2891-8 PMID: 9611233
  68. 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
  69. A family of splice variants of CstF-64 expressed in vertebrate nervous systems.
    BMC Mol Biol. 2009 Mar 12;10:22 PMID: 19284619
  70. Alternative polyadenylation of cyclooxygenase-2.
    Nucleic Acids Res. 2005 May 04;33(8):2565-79 PMID: 15872218
  71. Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites.
    Science. 2008 Jun 20;320(5883):1643-7 PMID: 18566288
Article Info
Journal
Wiley interdisciplinary reviews. RNA
Abbr.
Wiley Interdiscip Rev RNA
ISSN
1757-7012
DOI
10.1002/wrna.47
Email
lutzcs@umdnj.edu
Published
2011-00-00
Pages
23-31
Language
English
Region
United States
NLM ID
101536955
PMCID
PMC3029013
Subset
IM
Grants
NICHD NIH HHS · 5R03HD054559-02 · United States
NHGRI NIH HHS · 5R21HG005129-02 · United States
NICHD NIH HHS · R03 HD054559-02 · United States
NICHD NIH HHS · R03 HD054559 · United States
NHGRI NIH HHS · R21 HG005129-01 · United States
NHGRI NIH HHS · R21 HG005129 · United States
External Links
PubMed source DOI: 10.1002/wrna.47 PMC Full Text View journal details
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