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. 1986 Mar;83(6):1568–1572. doi: 10.1073/pnas.83.6.1568

Large introns in the 3' end of the gene for the pro alpha 1 (IV) chain of human basement membrane collagen.

R Soininen, L Tikka, L Chow, T Pihlajaniemi, M Kurkinen, D J Prockop, C D Boyd, K Tryggvason
PMCID: PMC323124  PMID: 3006056

Abstract

Using a recently characterized cDNA clone (HT-21) coding for the pro alpha 1 (IV) chain of human type IV procollagen, we have isolated three clones from a bacterio-phage lambda Charon 4A library of human genomic DNA. The intron/exon structure of the pro alpha 1 (IV) genomic clones was analyzed by heteroduplex electron microscopy and nucleotide sequencing. The analysis showed that the introns separating exons 2-9 are large and have a total length of over 12,000 base pairs (bp). Six of seven exons at the 3' end of the gene coded for -Gly-Xaa-Yaa-repeats of the collagenous part of the chain. Five of the -Gly-Xaa-Yaa- coding exons (numbers 5-9) varied in size between 72 bp and 134 bp, and none of them were 54 bp or multiples thereof. A sixth exon (exon 4) was a junction exon containing 71 bp coding for -Gly-Xaa-Yaa- sequences and 142 bp coding for the carboxyl-terminal noncollagenous domain (NC-1). The seventh exon (exon 3, 178 bp) coded for sequences of the NC-1 domain. Five of the six -Gly-Xaa-Yaa- coding exons began with the second base coding for glycine, and only one exon began with a complete glycine codon at the 5' end. The results (i) suggest that the gene for the pro alpha 1(IV) chain of human basement membrane collagen is significantly larger than the genes for fibrillar collagens and (ii) show that it lacks the 54-bp exon repeats characteristic of fibrillar collagen genes.

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Selected References

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  1. Babel W., Glanville R. W. Structure of human-basement-membrane (type IV) collagen. Complete amino-acid sequence of a 914-residue-long pepsin fragment from the alpha 1(IV) chain. Eur J Biochem. 1984 Sep 17;143(3):545–556. doi: 10.1111/j.1432-1033.1984.tb08404.x. [DOI] [PubMed] [Google Scholar]
  2. Bentz H., Morris N. P., Murray L. W., Sakai L. Y., Hollister D. W., Burgeson R. E. Isolation and partial characterization of a new human collagen with an extended triple-helical structural domain. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3168–3172. doi: 10.1073/pnas.80.11.3168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernard M. P., Chu M. L., Myers J. C., Ramirez F., Eikenberry E. F., Prockop D. J. Nucleotide sequences of complementary deoxyribonucleic acids for the pro alpha 1 chain of human type I procollagen. Statistical evaluation of structures that are conserved during evolution. Biochemistry. 1983 Oct 25;22(22):5213–5223. doi: 10.1021/bi00291a023. [DOI] [PubMed] [Google Scholar]
  4. Boyd C. D., Tolstoshev P., Schafer M. P., Trapnell B. C., Coon H. C., Kretschmer P. J., Nienhuis A. W., Crystal R. G. Isolation and characterization of a 15-kilobase genomic sequence coding for part of the Pro alpha 2 chain of sheep type I collagen. J Biol Chem. 1980 Apr 10;255(7):3212–3220. [PubMed] [Google Scholar]
  5. Brinker J. M., Gudas L. J., Loidl H. R., Wang S. Y., Rosenbloom J., Kefalides N. A., Myers J. C. Restricted homology between human alpha 1 type IV and other procollagen chains. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3649–3653. doi: 10.1073/pnas.82.11.3649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Broek D. L., Madri J., Eikenberry E. F., Brodsky B. Characterization of the tissue form of type V collagen from chick bone. J Biol Chem. 1985 Jan 10;260(1):555–562. [PubMed] [Google Scholar]
  7. Cheah K. S., Stoker N. G., Griffin J. R., Grosveld F. G., Solomon E. Identification and characterization of the human type II collagen gene (COL2A1). Proc Natl Acad Sci U S A. 1985 May;82(9):2555–2559. doi: 10.1073/pnas.82.9.2555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chow L. T., Broker T. R., Lewis J. B. Complex splicing patterns of RNAs from the early regions of adenovirus-2. J Mol Biol. 1979 Oct 25;134(2):265–303. doi: 10.1016/0022-2836(79)90036-6. [DOI] [PubMed] [Google Scholar]
  9. Chu M. L., Weil D., de Wet W., Bernard M., Sippola M., Ramirez F. Isolation of cDNA and genomic clones encoding human pro-alpha 1 (III) collagen. Partial characterization of the 3' end region of the gene. J Biol Chem. 1985 Apr 10;260(7):4357–4363. [PubMed] [Google Scholar]
  10. Chu M. L., de Wet W., Bernard M., Ding J. F., Morabito M., Myers J., Williams C., Ramirez F. Human pro alpha 1(I) collagen gene structure reveals evolutionary conservation of a pattern of introns and exons. 1984 Jul 26-Aug 1Nature. 310(5975):337–340. doi: 10.1038/310337a0. [DOI] [PubMed] [Google Scholar]
  11. Jander R., Rauterberg J., Voss B., von Bassewitz D. B. A cysteine-rich collagenous protein from bovine placenta. Isolation of its constituent polypeptide chains and some properties of the non-denatured protein. Eur J Biochem. 1981;114(1):17–25. [PubMed] [Google Scholar]
  12. Kramer J. M., Cox G. N., Hirsh D. Comparisons of the complete sequences of two collagen genes from Caenorhabditis elegans. Cell. 1982 Sep;30(2):599–606. doi: 10.1016/0092-8674(82)90256-2. [DOI] [PubMed] [Google Scholar]
  13. Kurkinen M., Barlow D. P., Helfman D. M., Williams J. G., Hogan B. L. Isolation of cDNA clones for basal lamina components: type IV procollagen. Nucleic Acids Res. 1983 Sep 24;11(18):6199–6209. doi: 10.1093/nar/11.18.6199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurkinen M., Bernard M. P., Barlow D. P., Chow L. T. Characterization of 64-, 123- and 182-base-pair exons in the mouse alpha 2(IV) collagen gene. Nature. 1985 Sep 12;317(6033):177–179. doi: 10.1038/317177a0. [DOI] [PubMed] [Google Scholar]
  15. Lopata M. A., Havercroft J. C., Chow L. T., Cleveland D. W. Four unique genes required for beta tubulin expression in vertebrates. Cell. 1983 Mar;32(3):713–724. doi: 10.1016/0092-8674(83)90057-0. [DOI] [PubMed] [Google Scholar]
  16. Lozano G., Ninomiya Y., Thompson H., Olsen B. R. A distinct class of vertebrate collagen genes encodes chicken type IX collagen polypeptides. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4050–4054. doi: 10.1073/pnas.82.12.4050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  18. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  19. Monson J. M., McCarthy B. J. Identification of a Balb/c mouse pro alpha 1(I) procollagen gene: evidence for insertions or deletions in gene coding sequences. DNA. 1981;1(1):59–69. doi: 10.1089/dna.1.1981.1.59. [DOI] [PubMed] [Google Scholar]
  20. Monson J. M., Natzle J., Friedman J., McCarthy B. J. Expression and novel structure of a collagen gene in Drosophila. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1761–1765. doi: 10.1073/pnas.79.6.1761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Myers J. C., Dickson L. A., de Wet W. J., Bernard M. P., Chu M. L., Di Liberto M., Pepe G., Sangiorgi F. O., Ramirez F. Analysis of the 3' end of the human pro-alpha 2(I) collagen gene. Utilization of multiple polyadenylation sites in cultured fibroblasts. J Biol Chem. 1983 Aug 25;258(16):10128–10135. [PubMed] [Google Scholar]
  22. Oberbäumer I., Laurent M., Schwarz U., Sakurai Y., Yamada Y., Vogeli G., Voss T., Siebold B., Glanville R. W., Kühn K. Amino acid sequence of the non-collagenous globular domain (NC1) of the alpha 1(IV) chain of basement membrane collagen as derived from complementary DNA. Eur J Biochem. 1985 Mar 1;147(2):217–224. doi: 10.1111/j.1432-1033.1985.tb08739.x. [DOI] [PubMed] [Google Scholar]
  23. Pihlajaniemi T., Tryggvason K., Myers J. C., Kurkinen M., Lebo R., Cheung M. C., Prockop D. J., Boyd C. D. cDNA clones coding for the pro-alpha1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain. J Biol Chem. 1985 Jun 25;260(12):7681–7687. [PubMed] [Google Scholar]
  24. Prockop D. J., Kivirikko K. I. Heritable diseases of collagen. N Engl J Med. 1984 Aug 9;311(6):376–386. doi: 10.1056/NEJM198408093110606. [DOI] [PubMed] [Google Scholar]
  25. Sage H., Trüeb B., Bornstein P. Biosynthetic and structural properties of endothelial cell type VIII collagen. J Biol Chem. 1983 Nov 10;258(21):13391–13401. [PubMed] [Google Scholar]
  26. Sandell L. J., Yamada Y., Dorfman A., Upholt W. B. Identification of genomic DNA coding for chicken type II procollagen. J Biol Chem. 1983 Oct 10;258(19):11617–11621. [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sangiorgi F. O., Benson-Chanda V., de Wet W. J., Sobel M. E., Ramirez F. Analysis of cDNA and genomic clones coding for the pro alpha 1 chain of calf type II collagen. Nucleic Acids Res. 1985 Apr 25;13(8):2815–2826. doi: 10.1093/nar/13.8.2815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schmid T. M., Linsenmayer T. F. Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues. J Cell Biol. 1985 Feb;100(2):598–605. doi: 10.1083/jcb.100.2.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sippola M., Kaffe S., Prockop D. J. A heterozygous defect for structurally altered pro-alpha 2 chain of type I procollagen in a mild variant of osteogenesis imperfecta. The altered structure decreases the thermal stability of procollagen and makes it resistant to procollagen N-proteinase. J Biol Chem. 1984 Nov 25;259(22):14094–14100. [PubMed] [Google Scholar]
  31. Steinmann B., Tuderman L., Peltonen L., Martin G. R., McKusick V. A., Prockop D. J. Evidence for a structural mutation of procollagen type I in a patient with the Ehlers-Danlos syndrome type VII. J Biol Chem. 1980 Sep 25;255(18):8887–8893. [PubMed] [Google Scholar]
  32. Tate V. E., Finer M. H., Boedtker H., Doty P. Chick pro alpha 2 (I) collagen gene: exon location and coding potential for the prepropeptide. Nucleic Acids Res. 1983 Jan 11;11(1):91–104. doi: 10.1093/nar/11.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tate V., Finer M., Boedtker H., Doty P. Procollagen genes: further sequence studies and interspecies comparisons. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):1039–1049. doi: 10.1101/sqb.1983.047.01.117. [DOI] [PubMed] [Google Scholar]
  34. Timpl R., Wiedemann H., van Delden V., Furthmayr H., Kühn K. A network model for the organization of type IV collagen molecules in basement membranes. Eur J Biochem. 1981 Nov;120(2):203–211. doi: 10.1111/j.1432-1033.1981.tb05690.x. [DOI] [PubMed] [Google Scholar]
  35. Tryggvason K., Robey P. G., Martin G. R. Biosynthesis of type IV procollagens. Biochemistry. 1980 Apr 1;19(7):1284–1289. doi: 10.1021/bi00548a003. [DOI] [PubMed] [Google Scholar]
  36. Wang S. Y., Gudas L. J. Isolation of cDNA clones specific for collagen IV and laminin from mouse teratocarcinoma cells. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5880–5884. doi: 10.1073/pnas.80.19.5880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams C. J., Prockop D. J. Synthesis and processing of a type I procollagen containing shortened pro-alpha 1(I) chains by fibroblasts from a patient with osteogenesis imperfecta. J Biol Chem. 1983 May 10;258(9):5915–5921. [PubMed] [Google Scholar]
  38. Yamada Y., Avvedimento V. E., Mudryj M., Ohkubo H., Vogeli G., Irani M., Pastan I., de Crombrugghe B. The collagen gene: evidence for its evolutinary assembly by amplification of a DNA segment containing an exon of 54 bp. Cell. 1980 Dec;22(3):887–892. doi: 10.1016/0092-8674(80)90565-6. [DOI] [PubMed] [Google Scholar]
  39. Yamada Y., Liau G., Mudryj M., Obici S., de Crombrugghe B. Conservation of the sizes for one but not another class of exons in two chick collagen genes. 1984 Jul 26-Aug 1Nature. 310(5975):333–337. doi: 10.1038/310333a0. [DOI] [PubMed] [Google Scholar]
  40. van der Rest M., Mayne R., Ninomiya Y., Seidah N. G., Chretien M., Olsen B. R. The structure of type IX collagen. J Biol Chem. 1985 Jan 10;260(1):220–225. [PubMed] [Google Scholar]

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