Logo of narLink to Publisher's site
Nucleic Acids Res. Nov 1, 1997; 25(21): 4296–4300.
PMCID: PMC147039

Expression of the thyroid hormone receptor gene, erbAalpha, in B lymphocytes: alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels.


The erbAalpha gene encodes two alpha-thyroid hormone receptor isoforms, TRalpha1 and TRalpha2, which arise from alternatively processed mRNAs, erbAalpha1 (alpha1) and erb alpha2 (alpha2). The splicing and alternative polyadenylation patterns of these mRNAs resemble that of mRNAs encoding different forms of immunoglobulin heavy chains, which are regulated at the level of alternative processing during B cell differentiation. This study examines the levels of erbAalpha mRNA in eight B cell lines representing four stages of differentiation in order to determine whether regulation of the alternatively processed alpha1 and alpha2 mRNAs parallels the processing of immunoglobulin heavy chain mRNAs. Results show that the pattern of alpha1 and alpha2 mRNA expression is clearly different from that observed for immunoglobulin heavy chain mRNAs. B cell lines display characteristic ratios of alpha1/alpha2 mRNA at distinct stages of differentiation. Furthermore, expression of an overlapping gene, Rev-ErbAalpha (RevErb), was found to correlate strongly with an increase in the ratio of alpha1/alpha2 mRNA. These results suggest that alternative processing of erbAalpha mRNAs is regulated by a mechanism which is distinct from that regulating immunoglobulin mRNA. The correlation between RevErb and erbAalpha mRNA is consistent with negative regulation of alpha2 via antisense interactions with the complementary RevErb mRNA.

Full Text

The Full Text of this article is available as a PDF (128K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sap J, Muñoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H, Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. [PubMed]
  • Weinberger C, Thompson CC, Ong ES, Lebo R, Gruol DJ, Evans RM. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. [PubMed]
  • Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. [PubMed]
  • Lazar MA. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev. 1993 Apr;14(2):184–193. [PubMed]
  • Benbrook D, Pfahl M. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987 Nov 6;238(4828):788–791. [PubMed]
  • Izumo S, Mahdavi V. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature. 1988 Aug 11;334(6182):539–542. [PubMed]
  • Mitsuhashi T, Tennyson GE, Nikodem VM. Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5804–5808. [PMC free article] [PubMed]
  • Katz D, Lazar MA. Dominant negative activity of an endogenous thyroid hormone receptor variant (alpha 2) is due to competition for binding sites on target genes. J Biol Chem. 1993 Oct 5;268(28):20904–20910. [PubMed]
  • Jannini EA, Mitsuhashi T, Nikodem VM. Developmental expression of mRNAs from a rat C-erbA genomic locus. Biochem Biophys Res Commun. 1992 Apr 30;184(2):739–745. [PubMed]
  • Leonard JL, Farwell AP, Yen PM, Chin WW, Stula M. Differential expression of thyroid hormone receptor isoforms in neurons and astroglial cells. Endocrinology. 1994 Aug;135(2):548–555. [PubMed]
  • Edwalds-Gilbert G, Veraldi KL, Milcarek C. Alternative poly(A) site selection in complex transcription units: means to an end? Nucleic Acids Res. 1997 Jul 1;25(13):2547–2561. [PMC free article] [PubMed]
  • Peterson ML. Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: non-Ig RNA can be alternatively processed in B cells and plasma cells. Mol Cell Biol. 1994 Dec;14(12):7891–7898. [PMC free article] [PubMed]
  • Edwalds-Gilbert G, Milcarek C. Regulation of poly(A) site use during mouse B-cell development involves a change in the binding of a general polyadenylation factor in a B-cell stage-specific manner. Mol Cell Biol. 1995 Nov;15(11):6420–6429. [PMC free article] [PubMed]
  • Matis SA, Martincic K, Milcarek C. B-lineage regulated polyadenylation occurs on weak poly(A) sites regardless of sequence composition at the cleavage and downstream regions. Nucleic Acids Res. 1996 Dec 1;24(23):4684–4692. [PMC free article] [PubMed]
  • Takagaki Y, Seipelt RL, Peterson ML, Manley JL. The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell. 1996 Nov 29;87(5):941–952. [PubMed]
  • Lazar MA, Hodin RA, Darling DS, Chin WW. A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit. Mol Cell Biol. 1989 Mar;9(3):1128–1136. [PMC free article] [PubMed]
  • Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T. Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell. 1989 Apr 7;57(1):31–39. [PubMed]
  • Kobrin BJ, Milcarek C, Morrison SL. Sequences near the 3' secretion-specific polyadenylation site influence levels of secretion-specific and membrane-specific IgG2b mRNA in myeloma cells. Mol Cell Biol. 1986 May;6(5):1687–1697. [PMC free article] [PubMed]
  • Genovese C, Harrold S, Milcarek C. Differential mRNA stabilities affect mRNA levels in mutant mouse myeloma cells. Somat Cell Mol Genet. 1991 Jan;17(1):69–81. [PubMed]
  • Katz D, Berrodin TJ, Lazar MA. The unique C-termini of the thyroid hormone receptor variant, c-erbA alpha 2, and thyroid hormone receptor alpha 1 mediate different DNA-binding and heterodimerization properties. Mol Endocrinol. 1992 May;6(5):805–814. [PubMed]
  • Peterson ML, Bryman MB, Peiter M, Cowan C. Exon size affects competition between splicing and cleavage-polyadenylation in the immunoglobulin mu gene. Mol Cell Biol. 1994 Jan;14(1):77–86. [PMC free article] [PubMed]
  • Lazar MA, Hodin RA, Cardona G, Chin WW. Gene expression from the c-erbA alpha/Rev-ErbA alpha genomic locus. Potential regulation of alternative splicing by opposite strand transcription. J Biol Chem. 1990 Aug 5;265(22):12859–12863. [PubMed]
  • Chawla A, Lazar MA. Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. J Biol Chem. 1993 Aug 5;268(22):16265–16269. [PubMed]
  • Munroe SH, Lazar MA. Inhibition of c-erbA mRNA splicing by a naturally occurring antisense RNA. J Biol Chem. 1991 Nov 25;266(33):22083–22086. [PubMed]
  • Hildebrandt M, Nellen W. Differential antisense transcription from the Dictyostelium EB4 gene locus: implications on antisense-mediated regulation of mRNA stability. Cell. 1992 Apr 3;69(1):197–204. [PubMed]
  • Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec 3;75(5):843–854. [PubMed]
  • Paavonen T. Enhancement of human B lymphocyte differentiation in vitro by thyroid hormone. Scand J Immunol. 1982 Feb;15(2):211–215. [PubMed]
  • Chatterjee S, Chandel AS. Immunomodulatory role of thyroid hormones: in vivo effect of thyroid hormones on the blastogenic response of lymphoid tissues. Acta Endocrinol (Copenh) 1983 May;103(1):95–100. [PubMed]
  • Csaba G, Sudár F. Differentiation dependent alterations in lymphocytic triiodothyronine reception. Horm Metab Res. 1978 Sep;10(5):455–456. [PubMed]
  • Grant PA, Thompson CB, Pettersson S. IgM receptor-mediated transactivation of the IgH 3' enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function. EMBO J. 1995 Sep 15;14(18):4501–4513. [PMC free article] [PubMed]
  • Pfahl M. Nuclear receptor/AP-1 interaction. Endocr Rev. 1993 Oct;14(5):651–658. [PubMed]
  • Saatcioglu F, Bartunek P, Deng T, Zenke M, Karin M. A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor). Mol Cell Biol. 1993 Jun;13(6):3675–3685. [PMC free article] [PubMed]
  • Zhang XK, Wills KN, Husmann M, Hermann T, Pfahl M. Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities. Mol Cell Biol. 1991 Dec;11(12):6016–6025. [PMC free article] [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...