Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 May;9(5):2114–2123. doi: 10.1128/mcb.9.5.2114

Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y.

K R Johnson 1, D A Lehn 1, R Reeves 1
PMCID: PMC363005  PMID: 2701943

Abstract

The high-mobility-group protein HMG-I is a well-characterized nonhistone chromosomal protein that is preferentially expressed in rapidly dividing cells, binds to A. T-rich regions of DNA in vitro, and has been localized to particular regions of mammalian metaphase chromosomes. We isolated eight cDNA clones encoding HMG-I and its isoform HMG-Y from a human Raji cell cDNA library and detected blocks of nucleotide sequence rearrangements in the 5'-untranslated regions of these clones. In addition to this leader sequence variation, five of the eight cDNA clones had either a 33- or 36-base-pair in-frame deletion in their open reading frame (ORF); we found that this shortened ORF encodes the HMG-Y protein isoform. We present evidence that the 5'-untranslated-region and ORF heterogeneity of the cDNA clones is the result of alternative processing of RNA transcripts from a single functional gene. Several additional but probably nonfunctional HMG-I or HMG-Y gene copies exist in the human genome; we isolated and partially sequenced one of these pseudogenes and found that it is a processed HMG-Y retropseudogene.

Full text

PDF
2114

Images in this article

2118Image
on p.2118
2118Image
on p.2118
2120Image
on p.2120

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Breitbart R. E., Andreadis A., Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. doi: 10.1146/annurev.bi.56.070187.002343. [DOI] [PubMed] [Google Scholar]
  2. Elton T. S., Reeves R. Microheterogeneity of the mammalian high mobility group (HMG) proteins 1 and 2 investigated by reverse-phase high performance liquid chromatography. Anal Biochem. 1985 Feb 1;144(2):403–416. doi: 10.1016/0003-2697(85)90133-2. [DOI] [PubMed] [Google Scholar]
  3. Elton T. S., Reeves R. Microheterogeneity of the mammalian high-mobility group proteins 14 and 17 investigated by reverse-phase high-performance liquid chromatography. Anal Biochem. 1985 May 1;146(2):448–460. doi: 10.1016/0003-2697(85)90568-8. [DOI] [PubMed] [Google Scholar]
  4. Elton T. S., Reeves R. Purification and postsynthetic modifications of Friend erythroleukemic cell high mobility group protein HMG-I. Anal Biochem. 1986 Aug 15;157(1):53–62. doi: 10.1016/0003-2697(86)90195-8. [DOI] [PubMed] [Google Scholar]
  5. Giancotti V., Pani B., D'Andrea P., Berlingieri M. T., Di Fiore P. P., Fusco A., Vecchio G., Philp R., Crane-Robinson C., Nicolas R. H. Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle T genes. EMBO J. 1987 Jul;6(7):1981–1987. doi: 10.1002/j.1460-2075.1987.tb02461.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodwin G. H., Cockerill P. N., Kellam S., Wright C. A. Fractionation by high-performance liquid chromatography of the low-molecular-mass high-mobility-group (HMG) chromosomal proteins present in proliferating rat cells and an investigation of the HMG proteins present in virus transformed cells. Eur J Biochem. 1985 May 15;149(1):47–51. doi: 10.1111/j.1432-1033.1985.tb08891.x. [DOI] [PubMed] [Google Scholar]
  7. Johnson K. R., Lehn D. A., Elton T. S., Barr P. J., Reeves R. Complete murine cDNA sequence, genomic structure, and tissue expression of the high mobility group protein HMG-I(Y). J Biol Chem. 1988 Dec 5;263(34):18338–18342. [PubMed] [Google Scholar]
  8. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kozak M. Bifunctional messenger RNAs in eukaryotes. Cell. 1986 Nov 21;47(4):481–483. doi: 10.1016/0092-8674(86)90609-4. [DOI] [PubMed] [Google Scholar]
  10. Leff S. E., Rosenfeld M. G., Evans R. M. Complex transcriptional units: diversity in gene expression by alternative RNA processing. Annu Rev Biochem. 1986;55:1091–1117. doi: 10.1146/annurev.bi.55.070186.005303. [DOI] [PubMed] [Google Scholar]
  11. Lehn D. A., Elton T. S., Johnson K. R., Reeves R. A conformational study of the sequence specific binding of HMG-I (Y) with the bovine interleukin-2 cDNA. Biochem Int. 1988 May;16(5):963–971. [PubMed] [Google Scholar]
  12. Lund T., Dahl K. H., Mørk E., Holtlund J., Laland S. G. The human chromosomal protein HMG I contains two identical palindrome amino acid sequences. Biochem Biophys Res Commun. 1987 Jul 31;146(2):725–730. doi: 10.1016/0006-291x(87)90589-4. [DOI] [PubMed] [Google Scholar]
  13. Lund T., Holtlund J., Fredriksen M., Laland S. G. On the presence of two new high mobility group-like proteins in HeLa S3 cells. FEBS Lett. 1983 Feb 21;152(2):163–167. doi: 10.1016/0014-5793(83)80370-6. [DOI] [PubMed] [Google Scholar]
  14. Nissen M. S., Friesen P. D. Molecular analysis of the transcriptional regulatory region of an early baculovirus gene. J Virol. 1989 Feb;63(2):493–503. doi: 10.1128/jvi.63.2.493-503.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
  16. Reeves R., Elton T. S., Nissen M. S., Lehn D., Johnson K. R. Posttranscriptional gene regulation and specific binding of the nonhistone protein HMG-I by the 3' untranslated region of bovine interleukin 2 cDNA. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6531–6535. doi: 10.1073/pnas.84.18.6531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Renshaw M. W., Capozza M. A., Wang J. Y. Differential expression of type-specific c-abl mRNAs in mouse tissues and cell lines. Mol Cell Biol. 1988 Oct;8(10):4547–4551. doi: 10.1128/mcb.8.10.4547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Russnak R. H., Candido E. P., Astell C. R. Interaction of the mouse chromosomal protein HMG-I with the 3' ends of genes in vitro. J Biol Chem. 1988 May 5;263(13):6392–6399. [PubMed] [Google Scholar]
  19. 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]
  20. Santoro C., Mermod N., Andrews P. C., Tjian R. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature. 1988 Jul 21;334(6179):218–224. doi: 10.1038/334218a0. [DOI] [PubMed] [Google Scholar]
  21. Solomon M. J., Strauss F., Varshavsky A. A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1276–1280. doi: 10.1073/pnas.83.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Srikantha T., Landsman D., Bustin M. Retropseudogenes for human chromosomal protein HMG-17. J Mol Biol. 1987 Oct 5;197(3):405–413. doi: 10.1016/0022-2836(87)90554-7. [DOI] [PubMed] [Google Scholar]
  23. Stroeher V. L., Gaiser J. C., Garber R. L. Alternative RNA splicing that is spatially regulated: generation of transcripts from the Antennapedia gene of Drosophila melanogaster with different protein-coding regions. Mol Cell Biol. 1988 Oct;8(10):4143–4154. doi: 10.1128/mcb.8.10.4143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Strubin M., Long E. O., Mach B. Two forms of the Ia antigen-associated invariant chain result from alternative initiations at two in-phase AUGs. Cell. 1986 Nov 21;47(4):619–625. doi: 10.1016/0092-8674(86)90626-4. [DOI] [PubMed] [Google Scholar]
  25. Vartiainen E., Palvimo J., Mahonen A., Linnala-Kankkunen A., Mäenpä P. H. Selective decrease in low-Mr HMG proteins HMG I and HMG Y during differentiation of mouse teratocarcinoma cells. FEBS Lett. 1988 Feb 8;228(1):45–48. doi: 10.1016/0014-5793(88)80581-7. [DOI] [PubMed] [Google Scholar]
  26. Weiner A. M., Deininger P. L., Efstratiadis A. Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem. 1986;55:631–661. doi: 10.1146/annurev.bi.55.070186.003215. [DOI] [PubMed] [Google Scholar]
  27. Yang-Yen H. F., Rothblum L. I. Purification and characterization of a high-mobility-group-like DNA-binding protein that stimulates rRNA synthesis in vitro. Mol Cell Biol. 1988 Aug;8(8):3406–3414. doi: 10.1128/mcb.8.8.3406. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES