title: The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue-specific expression.
abstract: The ribonuclease A (RNase A) superfamily has been the subject of extensive studies in the areas of protein evolution, structure and biochemistry and are exciting molecules in that they appear to be responding to unique selection pressures, generating proteins capable of multiple and diverse activities. The RNase 4 and RNase 5/ang 1 shared locus breaks a pattern that is otherwise canonical among the members of the RNase A gene superfamily. Conserved among humans, mice and rats, the locus includes two non-coding exons followed by two distinct exons encoding RNase 4 and RNase 5/ang 1. Transcription from this locus is controlled by differential splicing and tissue-specific expression from promoters located 5' to each of the non-coding exons. Promoter 1, 5' to exon I, is universally active, while Promoter 2, 5' to exon II, is active only in hepatic cells in promoter assays in vitro. Transcription from Promoter 2 is dependent on an intact HNF-1 consensus binding site which binds the transcription factor HNF-1alpha. In summary, RNase 4 and RNase 5/ang 1 are unique among the RNase A ribonuclease genes in that they maintain a complex gene locus that is conserved across species with transcription initiated from tissue-specific dual promoters followed by differential exon splicing.
authors.affiliation: Laboratory of Allergic Diseases NIAID, NIH, Bethesda, MD 20892, USA. kdyer@niaid.nih.gov
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000378:metabolism; D004722:Endoribonucleases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D051381:Rats; D012259:Ribonuclease, Pancreatic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D004722:Endoribonucleases; C497716:Rnase2b protein, mouse; C497715:Rnase4 protein, mouse; D012259:Ribonuclease, Pancreatic
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9838-42
references.pmid: 2263635
references.citation: Genes Dev. 1990 Mar;4(3):372-9
references.pmid: 1970973
references.citation: Protein Sci. 1994 Mar;3(3):459-66
references.pmid: 8019417
references.citation: Biochem J. 1995 Feb 1;305 ( Pt 3):921-7
references.pmid: 7531438
references.citation: Biochim Biophys Acta. 1995 Apr 26;1261(3):424-6
references.pmid: 7742370
references.citation: Nucleic Acids Res. 1995 Nov 11;23(21):4290-5
references.pmid: 7501448
references.citation: J Biol Chem. 1995 Dec 15;270(50):30234
references.pmid: 8530435
references.citation: J Biol Chem. 1996 May 24;271(21):12387-93
references.pmid: 8647842
references.citation: J Biol Chem. 1997 Jan 17;272(3):1665-9
references.pmid: 8999843
references.citation: Blood. 1998 Mar 15;91(6):2126-32
references.pmid: 9490699
references.citation: Mol Cell Biol. 1998 May;18(5):3059-68
references.pmid: 9566924
references.citation: J Clin Invest. 1998 May 15;101(10):2215-22
references.pmid: 9593777
references.citation: Biochim Biophys Acta. 1998 Apr 23;1384(1):55-65
references.pmid: 9602056
references.citation: Biochemistry. 1998 Jun 30;37(26):9250-7
references.pmid: 9649305
references.citation: Cell Mol Life Sci. 1998 Aug;54(8):763-5
references.pmid: 9760984
references.citation: Cell Mol Life Sci. 1998 Aug;54(8):811-24
references.pmid: 9760990
references.citation: Cell Mol Life Sci. 1998 Aug;54(8):825-32
references.pmid: 9760991
references.citation: Genes Immun. 2004 Dec;5(8):668-74
references.pmid: 15526002
references.citation: Genomics. 2005 Feb;85(2):208-20
references.pmid: 15676279
references.citation: J Mol Evol. 2004 Nov;59(5):657-65
references.pmid: 15693621
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4701-6
references.pmid: 10758160
references.citation: Hum Mutat. 2000 Nov;16(5):377-85
references.pmid: 11058894
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: J Mol Endocrinol. 2001 Aug;27(1):11-29
references.pmid: 11463573
references.citation: Diabetes. 2001 Nov;50(11):2472-80
references.pmid: 11679424
references.citation: J Leukoc Biol. 2001 Nov;70(5):691-8
references.pmid: 11698487
references.citation: Bioinformatics. 2001 Dec;17(12):1244-5
references.pmid: 11751241
references.citation: Nucleic Acids Res. 2002 Mar 1;30(5):1169-75
references.pmid: 11861908
references.citation: Nat Genet. 2002 Apr;30(4):411-5
references.pmid: 11925567
references.citation: Nat Immunol. 2003 Mar;4(3):269-73
references.pmid: 12548285
references.citation: J Immunol. 2003 Oct 15;171(8):4219-26
references.pmid: 14530345
references.citation: Mol Endocrinol. 2003 Nov;17(11):2138-51
references.pmid: 12920233
references.citation: J Immunol. 2003 Nov 15;171(10):5277-86
references.pmid: 14607929
references.citation: Biol Reprod. 2004 Feb;70(2):319-28
references.pmid: 14561640
references.citation: Mamm Genome. 2004 Feb;15(2):126-34
references.pmid: 15058383
references.citation: J Immunol. 1986 Nov 1;137(9):2913-7
references.pmid: 3760576
references.citation: Biochemistry. 1986 Nov 18;25(23):7255-64
references.pmid: 3467790
references.citation: Nucleic Acids Res. 1989 Feb 11;17(3):939-53
references.pmid: 2922278
references.citation: J Exp Med. 1989 Jul 1;170(1):163-76
references.pmid: 2473157
references.citation: J Biol Chem. 1991 Jan 15;266(2):677-80
references.pmid: 1985954