title: DAZAP1 regulates the splicing of Crem, Crisp2 and Pot1a transcripts.
abstract: Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous heterogeneous nuclear ribonucleoprotein (hnRNP) that is expressed abundantly in the testis. DAZAP1 deficiency in mice results in growth retardation and spermatogenic arrest. Previous reports on DAZAP1's binding to several naturally occurring splicing mutations support a role for DAZAP1 in RNA splicing. To elucidate the biological function(s) of DAZAP1 and to search for its natural RNA substrates, we used microarrays to compare the expression profiles and exon usages of wild-type and Dazap1 mutant testes and identified three genes (Crem, Crisp2 and Pot1a) with aberrant RNA splicing in the mutant testes. We further demonstrated that DAZAP1, but not DAZAP1 mutant proteins, promoted the inclusion of Crem exon 4, Crisp2 exon 9 and Pot1a exon 4 in splicing reporter transcripts in cultured cells. Additional studies on the binding of DAZAP1 to the exons and their flanking intronic sequences and the effects of minigene deletions on exon inclusion identified regulatory regions in Crem intron 3, Crisp2 intron 9 and Pot1a intron 4 where DAZAP1 bound and regulated splicing. Aberrant splicing of the Pot1a gene, which encodes an essential protein that protects telomere integrity, may partially account for the growth retardation phenotype of DAZAP1-deficient mice.
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan and Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors: Hsiang-Ying
authors: HY
authors: Chen
authors: Yueh-Hsiang
authors: YH
authors: Yu
authors: Pauline H
authors: PH
authors: Yen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins
chemical_list: D015815:Cell Adhesion Molecules; C497411:Crem protein, mouse; C483816:Crisp2 protein, mouse; D004268:DNA-Binding Proteins; C510165:Dazap1 protein, mouse; D006023:Glycoproteins; D008565:Membrane Proteins; C507326:POT1 protein, mouse; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D051786:Cyclic AMP Response Element Modulator
references: Nature. 1996 Mar 14;380(6570):162-5
references: 8600391
references: Nucleic Acids Res. 2005 Jan 12;33(1):190-200
references: 15647502
references: Cell. 2006 Jul 14;126(1):63-77
references: 16839877
references: Mamm Genome. 1992;3(5):274-80
references: 1638086
references: J Cell Biol. 1977 Jul;74(1):68-85
references: 874003
references: RNA. 2011 Jul;17(7):1282-95
references: 21576381
references: BMC Genomics. 2001;2:6
references: 11604102
references: Nature. 1992 Jan 2;355(6355):80-4
references: 1370576
references: Cell. 2006 Jul 14;126(1):49-62
references: 16839876
references: Nat Rev Genet. 2003 Aug;4(8):626-37
references: 12897774
references: Nature. 1996 Mar 14;380(6570):159-62
references: 8600390
references: FEBS Lett. 2008 Jun 25;582(15):2231-6
references: 18503770
references: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):20881-90
references: 22065782
references: EMBO J. 2012 Oct 17;31(20):4020-34
references: 22960638
references: Asian J Androl. 2011 Jan;13(1):111-7
references: 20972450
references: Nucleic Acids Res. 2004 Jun 24;32(11):e88
references: 15247321
references: Cancer Sci. 2004 Jun;95(6):503-7
references: 15182431
references: Nature. 2006 Nov 30;444(7119):580-6
references: 17065982
references: J Androl. 2002 Sep-Oct;23(5):622-8
references: 12185095
references: PLoS One. 2011;6(8):e23349
references: 21858080
references: Mol Cell Endocrinol. 2002 Feb 22;187(1-2):115-24
references: 11988318
references: Leukemia. 2005 May;19(5):806-13
references: 15744350
references: Genomics. 2000 May 1;65(3):266-73
references: 10857750
references: PLoS Genet. 2011 Dec;7(12):e1002390
references: 22194695
references: Mol Cell Biol. 2002 Nov;22(22):8079-87
references: 12391173
references: RNA. 2006 Aug;12(8):1486-93
references: 16772659
references: Genes Dev. 2005 Sep 15;19(18):2100-10
references: 16166375
references: RNA. 2008 Sep;14(9):1814-22
references: 18669443
references: Gene. 2012 Jan 1;491(1):13-9
references: 22001406
references: Mol Cell Biol. 2008 Sep;28(17):5403-19
references: 18573884
references: Curr Opin Cell Biol. 2005 Jun;17(3):309-15
references: 15901502
references: Biochem Biophys Res Commun. 2012 Nov 23;428(3):422-6
references: 23111326
references: Annu Rev Biochem. 1993;62:289-321
references: 8352591
references: FEBS J. 2011 Sep;278(18):3246-55
references: 21794093
references: Nat Struct Mol Biol. 2012 Oct;19(10):1044-52
references: 22983564
references: Anal Biochem. 2008 Apr 15;375(2):373-5
references: 18157935
references: Mol Cell Biol. 2008 Jun;28(11):3850-60
references: 18391021
references: Biochem Biophys Res Commun. 2009 Mar 13;380(3):705-9
references: 19285026
references: J Biol Chem. 2013 Jul 26;288(30):22141-9
references: 23760279
references: Cell. 1991 Feb 22;64(4):739-49
references: 1847666
references: Nat Rev Mol Cell Biol. 2009 Nov;10(11):741-54
references: 19773805
references: Genes Dev. 2010 Jun 1;24(11):1073-4
references: 20516191