Regulation of gene expression by alternative untranslated regions.

The untranslated regions of mRNAs can determine gene expression by influencing mRNA stability and translational efficiency. Recent reports show that gene expression can be regulated by the differential use of alternative untranslated regions. Tissue-specific expression of transcripts that have different untranslated regions (UTRs) can control protein expression enabling developmental, physiological and pathological regulation. Several examples of alternative UTRs have been characterized, including those found in AXIN2, FGF1 and BRCA1. Results from bioinformatics studies indicate that this mechanism is more common than previously appreciated.

[1]  P. Sil,et al.  Characterization and functional significance of myotrophin: a gene with multiple transcripts. , 2005, Gene.

[2]  D. Eichler,et al.  Endothelial Argininosuccinate Synthase mRNA 5′-Untranslated Region Diversity , 2002, The Journal of Biological Chemistry.

[3]  M. Kozak,et al.  An analysis of vertebrate mRNA sequences: intimations of translational control , 1991, The Journal of cell biology.

[4]  Bin Tian,et al.  Alternative polyadenylation of cyclooxygenase-2 , 2005, Nucleic acids research.

[5]  A. Roberts,et al.  An alternatively‐spliced exon in the 5′‐UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem‐mediated decay , 2005, FEBS letters.

[6]  G. Mize,et al.  Role of two upstream open reading frames in the translational control of oncogene mdm2 , 1999, Oncogene.

[7]  R. Labouriau,et al.  Molecular Characterization of Major Histocompatibility Complex Class I (B‐F) mRNA Variants from Chickens Differing in Resistance to Marek's Disease , 2005, Scandinavian journal of immunology.

[8]  C. Muller,et al.  Structure of the glucocorticoid receptor (NR3C1) gene 5' untranslated region: identification, and tissue distribution of multiple new human exon 1. , 2005, Journal of molecular endocrinology.

[9]  Hui Li Goh,et al.  Genomic organization of human arylamine N-acetyltransferase Type I reveals alternative promoters that generate different 5'-UTR splice variants with altered translational activities. , 2005, The Biochemical journal.

[10]  A. Varela-Echavarría,et al.  Regulatory role of the 3′ untranslated region (3′UTR) of rat 5′ deiodinase (D1). Effects on messenger RNA translation and stability , 2005, Endocrine.

[11]  R. Myers,et al.  Identification and functional analysis of human transcriptional promoters. , 2003, Genome research.

[12]  K. Sobczak,et al.  Structural Determinants of BRCA1 Translational Regulation* , 2002, The Journal of Biological Chemistry.

[13]  G. Gerton,et al.  Differential RNA expression and polyribosome loading of alternative transcripts of the Akap4 gene in murine spermatids , 2005, Molecular reproduction and development.

[14]  O. Gotoh,et al.  Species-specific variation of alternative splicing and transcriptional initiation in six eukaryotes. , 2005, Gene.

[15]  T. Osborne,et al.  HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions , 1984, Cell.

[16]  M. Greenwood,et al.  The mouse sphingomyelin synthase 1 (SMS1) gene is alternatively spliced to yield multiple transcripts and proteins. , 2005, Gene.

[17]  Philipp Kapranov,et al.  Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. , 2005, Genome research.

[18]  J. B. Park,et al.  Cloning, Sequencing, and Characterization of Alternatively Spliced Glutaredoxin 1 cDNA and Its Genomic Gene , 2005, Journal of Biological Chemistry.

[19]  T. Hughes,et al.  Expression of axin2 Is Regulated by the Alternative 5′-Untranslated Regions of Its mRNA* , 2005, Journal of Biological Chemistry.

[20]  Katherine E. M. Hoops,et al.  Two Discrete Promoters Regulate the Alternatively Spliced Human Interferon Regulatory Factor-5 Isoforms , 2005, Journal of Biological Chemistry.

[21]  D. Eichler,et al.  Regulation of Endothelial Argininosuccinate Synthase Expression and NO Production by an Upstream Open Reading Frame* , 2005, Journal of Biological Chemistry.

[22]  S. Limborska,et al.  Structural organization of the human complexin 2 gene (CPLX2) and aspects of its functional activity. , 2005, Gene.

[23]  M. Boguski,et al.  Evolutionary parameters of the transcribed mammalian genome: an analysis of 2,820 orthologous rodent and human sequences. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Qiang Wu,et al.  Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. , 2003, Genome research.

[25]  Sumio Sugano,et al.  Analysis of small human proteins reveals the translation of upstream open reading frames of mRNAs. , 2004, Genome research.

[26]  B. Semler,et al.  An internal ribosome entry site mediates translation of lymphoid enhancer factor-1. , 2005, RNA.

[27]  Viktoryia Sidarovich,et al.  Expression of the plasma prekallikrein gene: utilization of multiple transcription start sites and alternative promoter regions , 2005, Biological chemistry.

[28]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[29]  A. Prats,et al.  Internal Ribosome Entry Site Structural Motifs Conserved among Mammalian Fibroblast Growth Factor 1 Alternatively Spliced mRNAs , 2004, Molecular and Cellular Biology.

[30]  Dong Zhao,et al.  Rodent StAR mRNA is substantially regulated by control of mRNA stability through sites in the 3′-untranslated region and through coupling to ongoing transcription , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[31]  J. Juang,et al.  Distinct translation regulation by two alternative 5'UTRs of a stress-responsive protein--dPrx I. , 2005, Journal of biomedical science.

[32]  R. Moor,et al.  Translational Regulation of MOS Messenger RNA in Pig Oocytes1 , 2005, Biology of reproduction.

[33]  N. Sonenberg,et al.  Alternative splicing facilitates internal ribosome entry on the ornithine decarboxylase mRNA , 2005, Cellular and Molecular Life Sciences CMLS.

[34]  A. Willis,et al.  The implications of structured 5' untranslated regions on translation and disease. , 2005, Seminars in cell & developmental biology.

[35]  M. Nambiar,et al.  Decreased Stability and Translation of T Cell Receptor ζ mRNA with an Alternatively Spliced 3′-Untranslated Region Contribute to ζ Chain Down-regulation in Patients with Systemic Lupus Erythematosus* , 2005, Journal of Biological Chemistry.

[36]  Graziano Pesole,et al.  uAUG and uORFs in human and rodent 5'untranslated mRNAs. , 2005, Gene.

[37]  T. Rosol,et al.  Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability. , 2004, Journal of molecular endocrinology.

[38]  D. Morris,et al.  Upstream Open Reading Frames as Regulators of mRNA Translation , 2000, Molecular and Cellular Biology.

[39]  David R. Setzer,et al.  Size heterogeneity in the 3′ end of dihydrofolate reductase messenger RNAs in mouse cells , 1980, Cell.

[40]  S. Koyano,et al.  5′ Diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site , 2005, Molecular and Cellular Biochemistry.

[41]  M. Zamora,et al.  Translation of Eukaryotic Translation Initiation Factor 4GI (eIF4GI) Proceeds from Multiple mRNAs Containing a Novel Cap-dependent Internal Ribosome Entry Site (IRES) That Is Active during Poliovirus Infection* , 2005, Journal of Biological Chemistry.

[42]  M. Meisler,et al.  Multiple transcripts of sodium channel SCN8A (Na(V)1.6) with alternative 5'- and 3'-untranslated regions and initial characterization of the SCN8A promoter. , 2005, Genomics.

[43]  F. Dietrich,et al.  Identification and characterization of upstream open reading frames (uORF) in the 5′ untranslated regions (UTR) of genes in Saccharomyces cerevisiae , 2005, Current Genetics.

[44]  L. Krushel,et al.  Internal initiation of translation of the TrkB mRNA is mediated by multiple regions within the 5′ leader , 2005, Nucleic acids research.

[45]  Andrew C. Li,et al.  The mouse CCR2 gene is regulated by two promoters that are responsive to plasma cholesterol and peroxisome proliferator-activated receptor gamma ligands. , 2005, Biochemical and biophysical research communications.

[46]  R. Werner,et al.  Variable promoter usage and alternative splicing in five mouse connexin genes. , 2005, Genomics.

[47]  A Cestelli,et al.  RNA-protein interactions in the control of stability and localization of messenger RNA (review). , 2000, International journal of molecular medicine.

[48]  P. Tam,et al.  Distinct expression profiles of Mecp2 transcripts with different lengths of 3'UTR in the brain and visceral organs during mouse development. , 2005, Genomics.

[49]  Michael Ho,et al.  Expression of DHX32 in lymphoid tissues. , 2005, Experimental and molecular pathology.

[50]  G. Storz,et al.  An abundance of RNA regulators. , 2005, Annual review of biochemistry.

[51]  T. Hughes,et al.  Regulation of axin2 expression at the levels of transcription, translation and protein stability in lung and colon cancer. , 2006, Cancer letters.

[52]  E. J. Lee,et al.  Alternative promotion of the mouse acyl-CoA synthetase 6 (mAcsl6) gene mediates the expression of multiple transcripts with 5'-end heterogeneity: genetic organization of mAcsl6 variants. , 2005, Biochemical and biophysical research communications.

[53]  T. Hughes,et al.  E2F1 up-regulates the expression of the tumour suppressor axin2 both by activation of transcription and by mRNA stabilisation. , 2005, Biochemical and biophysical research communications.

[54]  C. Gissi,et al.  Structural and functional features of eukaryotic mRNA untranslated regions. , 2001, Gene.