Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1989 Oct; 9(10): 4402–4408.
PMCID: PMC362522

An intronic 10-base-pair deletion in a class II A beta gene affects RNA processing.


Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52, 1986; R. Reeves, T.S. Elton, M.S. Nissen, D. Lehn, and K.R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H.A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (A beta d) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished A beta d gene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5' of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified A beta-specific cDNA demonstrated that the small number of A beta d transcripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ben-Nun A, Choi E, McIntyre KR, Leeman SA, McKean DJ, Seidman JG, Glimcher LH. DNA-mediated transfer of major histocompatibility class II I-Ab and I-Abm12 genes into B lymphoma cells: molecular and functional analysis of introduced antigens. J Immunol. 1985 Aug;135(2):1456–1464. [PubMed]
  • Brawerman G. Determinants of messenger RNA stability. Cell. 1987 Jan 16;48(1):5–6. [PubMed]
  • Buchman AR, Berg P. Comparison of intron-dependent and intron-independent gene expression. Mol Cell Biol. 1988 Oct;8(10):4395–4405. [PMC free article] [PubMed]
  • Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Choi E, McIntyre K, Germain RN, Seidman JG. Murine I-A beta chain polymorphism: nucleotide sequences of three allelic I-A beta genes. Science. 1983 Jul 15;221(4607):283–286. [PubMed]
  • Cohen JB, Levinson AD. A point mutation in the last intron responsible for increased expression and transforming activity of the c-Ha-ras oncogene. Nature. 1988 Jul 14;334(6178):119–124. [PubMed]
  • Gerster T, Picard D, Schaffner W. During B-cell differentiation enhancer activity and transcription rate of immunoglobulin heavy chain genes are high before mRNA accumulation. Cell. 1986 Apr 11;45(1):45–52. [PubMed]
  • Glimcher LH, McKean DJ, Choi E, Seidman JG. Complex regulation of class II gene expression: analysis with class II mutant cell lines. J Immunol. 1985 Nov;135(5):3542–3550. [PubMed]
  • Groudine M, Peretz M, Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. [PMC free article] [PubMed]
  • Gubler U, Hoffman BJ. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. [PubMed]
  • Larhammar D, Hammerling U, Denaro M, Lund T, Flavell RA, Rask L, Peterson PA. Structure of the murine immune response I-A beta locus: sequence of the I-A beta gene and an adjacent beta-chain second domain exon. Cell. 1983 Aug;34(1):179–188. [PubMed]
  • Malissen M, Hunkapiller T, Hood L. Nucleotide sequence of a light chain gene of the mouse I-A subregion: A beta d. Science. 1983 Aug 19;221(4612):750–754. [PubMed]
  • Maniatis T, Reed R. The role of small nuclear ribonucleoprotein particles in pre-mRNA splicing. Nature. 1987 Feb 19;325(6106):673–678. [PubMed]
  • Mattaj IW. A binding consensus: RNA-protein interactions in splicing, snRNPs, and sex. Cell. 1989 Apr 7;57(1):1–3. [PubMed]
  • Nguyen HT, Medford RM, Nadal-Ginard B. Reversibility of muscle differentiation in the absence of commitment: analysis of a myogenic cell line temperature-sensitive for commitment. Cell. 1983 Aug;34(1):281–293. [PubMed]
  • Oi VT, Morrison SL, Herzenberg LA, Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. [PMC free article] [PubMed]
  • Padgett RA, Grabowski PJ, Konarska MM, Seiler S, Sharp PA. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. [PubMed]
  • Piechaczyk M, Blanchard JM, Marty L, Dani C, Panabieres F, El Sabouty S, Fort P, Jeanteur P. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acids Res. 1984 Sep 25;12(18):6951–6963. [PMC free article] [PubMed]
  • Raj NB, Pitha PM. Two levels of regulation of beta-interferon gene expression in human cells. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3923–3927. [PMC free article] [PubMed]
  • Reed R, Maniatis T. Intron sequences involved in lariat formation during pre-mRNA splicing. Cell. 1985 May;41(1):95–105. [PubMed]
  • Reeves R, Elton TS, Nissen MS, Lehn D, Johnson KR. 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. [PMC free article] [PubMed]
  • Reeves R, Spies AG, Nissen MS, Buck CD, Weinberg AD, Barr PJ, Magnuson NS, Magnuson JA. Molecular cloning of a functional bovine interleukin 2 cDNA. Proc Natl Acad Sci U S A. 1986 May;83(10):3228–3232. [PMC free article] [PubMed]
  • Rouault TA, Hentze MW, Caughman SW, Harford JB, Klausner RD. Binding of a cytosolic protein to the iron-responsive element of human ferritin messenger RNA. Science. 1988 Sep 2;241(4870):1207–1210. [PubMed]
  • Ruskin B, Greene JM, Green MR. Cryptic branch point activation allows accurate in vitro splicing of human beta-globin intron mutants. Cell. 1985 Jul;41(3):833–844. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Scharf SJ, Horn GT, Erlich HA. Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science. 1986 Sep 5;233(4768):1076–1078. [PubMed]
  • Sharp PA. Splicing of messenger RNA precursors. Science. 1987 Feb 13;235(4790):766–771. [PubMed]
  • Shaw G, Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. [PubMed]
  • Shaw P, Sordat B, Schibler U. Developmental coordination of alpha-amylase and psp gene expression during mouse parotid gland differentiation is controlled posttranscriptionally. Cell. 1986 Oct 10;47(1):107–112. [PubMed]
  • Swanson MS, Dreyfuss G. RNA binding specificity of hnRNP proteins: a subset bind to the 3' end of introns. EMBO J. 1988 Nov;7(11):3519–3529. [PMC free article] [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PMC free article] [PubMed]
  • Young HA, Varesio L, Hwu P. Posttranscriptional control of human gamma interferon gene expression in transfected mouse fibroblasts. Mol Cell Biol. 1986 Jun;6(6):2253–2256. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence and PMC links.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • Protein
    Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...