Biopolym. Cell. 1987; 3(3):115-127.
Ambiguity of the transcription boundaries of eucaryotic genes
1Kavsan V. M.
  1. Institute of Molecular Biology and Genetics, Academy of Sciences of the Ukrainian SSR
    Kiev, USSR


A great number of experimental data testify to a more complicated-mechanism of the eucaryotic mRNA generation as compared to that of procaryotic mRNAs. The latter have a transcription process which begins and terminates in the sites corresponding to 5'- and 3'-ends of functional mRNAs. The nuclear cells appear to have special control mechanisms of differential gene expression by selecting sites for initiation and termination of the transcription and/or for polyadenylation of mRNAs.


[1] Coutelle C. The precursor to animal cell messenger RNA. Biochem J. 1981;197(1):1-6.
[2] Kavsan VM. Formation of globin gene families as a model of eukaryotic gene formation. Mol Biol (Mosk). 1983;17(1):6-32.
[3] Williamson R, Drewienkiewicz CE, Paul J. Globin messenger sequences in high molecular weight RNA from embryonic mouse liver. Nat New Biol. 1973;241(107):66-8.
[4] Imaizumi T, Diggelmann H, Scherrer K. Demonstration of globin messenger sequences in giant nuclear precursors of messenger RNA of avian erythroblasts. Proc Natl Acad Sci U S A. 1973;70(4):1122-6.
[5] Spohr G, Imaizumi T, Scherrer K. Synthesis and processing of nuclear precursor-messenger RNA in avian erythroblasts and HeLa cells. Proc Natl Acad Sci U S A. 1974;71(12):5009-13.
[6] Niessing J. Globin messenger precursor RNA in duck immature red blood cells. Eur J Biochem. 1978;91(2):587-98.
[7] Hayashi Y, Mikami EI. Precursors of globin mRNA in erythroid-enriched bone marrow cells of mouse. J Biochem. 1978;83(3):699-709.
[8] Reynaud CA, Imaizumi-Scherrer MT, Scherrer K. Size determination of the transcriptional units of the avian globin genes defined at the pre-messenger RNA level. Formation of messenger RNA in eucaryotic cells : Abstr. IV Arolla Workshop. Arolla, 1980:91.
[9] Therwath A, Mengod G, Scherrer K. Transcription of globin genes in AEV transformed erythroblasts. Abstr. IV Arolla Workshop. Arolla, 1980:107.
[10] Reynaud CA, Imaizumi-Scherrer MT, Scherrer K. The size of the transcriptional units of the avian globin genes defined at the pre-messenger RNA level. J Mol Biol. 1980;140(4):481-504.
[11] Strair RK, Skoultchi AI, Shafritz DA. A characterization of globin mRNA sequences in the nucleus of duck immature red blood cells. Cell. 1977;12(1):133-41.
[12] Ross J. Purification and structural properties of the precursors of the globin messenger RNAs. J Mol Biol. 1978;119(1):21-35.
[13] Shaul Y, Kaminchik J, Aviv H. Large globin RNA molecules and their processing. Eur J Biochem. 1981;116(3):461-6.
[14] Bastos RN, Aviv H. Globin RNA precursor molecules: biosynthesis and process in erythroid cells. Cell. 1977;11(3):641-50.
[15] Haynes JR, Kalb VF Jr, Rosteck P Jr, Lingrel JB. The absence of a precursor larger than 16 S to globin mRNA. FEBS Lett. 1978;91(2):173-7.
[16] Kessler-Icekson G, Moreau J, Scherrer K. Isolation of globin pre-messenger RNA on thiol-agarose by terminally mercurated complementary DNA. Mol Biol Rep. 1981;7(1-3):83-92.
[17] Rohrbaugh ML, Hardison RC. Analysis of rabbit beta-like globin gene transcripts during development. J Mol Biol. 1983;164(3):395-417.
[18] Kavsan VM. Synthesis and structure of globin genes and insulin: Author. dis. ... Dr. biol. nauk. M., 1985. 43p.
[19] Zolotukhin SB, Kavsan VM. Globin-specific nuclear RNA of erythroid cells from the rabbit bone marrow. Biopolym. Cell. 1985; 1(4):208-213.
[20] Zolotukhin SB, Kashuba VI, Koval AP, Kavsan VM. Rabbit globin gene transcription: the multiplicity of termination sites. V Biochem. Congress: Abstracts book. Kiev, 1985; 2:355.
[21] Zolotukhin SB, Kavsan VM. Ambiguity of transcription boundaries of eucaryotic genes. Macromolecules in the functioning cell: Abstr. 4th symp. USSR-Italy (Kiev, 1984). Kiev : Naukova dumka, 1984:117.
[22] Fraser NW, Nevins JR, Ziff E, Darnell JE Jr. The major late adenovirus type-2 transcription unit: termination is downstream from the last poly(A) site. J Mol Biol. 1979;129(4):643-56.
[23] Nevins JR, Blanchard JM, Darnell JE Jr. Transcription units of adenovirus type 2. Termination of transcription beyond the poly(A) addition site in early regions 2 and 4. J Mol Biol. 1980;144(3):377-86.
[24] Ford JP, Hsu MT. Transcription pattern of in vivo-labeled late simian virus 40 RNA: equimolar transcription beyond the mRNA 3' terminus. J Virol. 1978;28(3):795-801.
[25] Hofer E, Darnell JE Jr. The primary transcription unit of the mouse beta-major globin gene. Cell. 1981;23(2):585-93.
[26] Citron B, Falck-Pedersen E, Salditt-Georgieff M, Darnell JE Jr. Transcription termination occurs within a 1000 base pair region downstream from the poly(A) site of the mouse beta-globin (major) gene. Nucleic Acids Res. 1984;12(22):8723-31.
[27] Solotuchin S. B., Koval A. P., Kavsan V. M. Bidirectional in vivo transcription of DNA segment downstream of the rabbit b-globin gene. 9 t h Nucle(ol)ar Work Shop (Krakow, 13-17 September, 1985). Krakow, 1985:47.
[28] Hagenbüchle O, Bovey R, Young RA. Tissue-specific expression of mouse-alpha-amylase genes: nucleotide sequence of isoenzyme mRNAs from pancreas and salivary gland. Cell. 1980;21(1):179-87.
[29] LeMeur M, Glanville N, Mandel JL, Gerlinger P, Palmiter R, Chambon P. The ovalbumin gene family: hormonal control of X and Y gene transcription and mRNA accumulation. Cell. 1981;23(2):561-71.
[30] Hamer DH, Leder P. Expression of the chromosomal mouse Beta maj-globin gene cloned in SV40. Nature. 1979;281(5726):35-40.
[31] Early P, Rogers J, Davis M, Calame K, Bond M, Wall R, Hood L. Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways. Cell. 1980;20(2):313-9.
[32] Fitzmaurice L, Owens J, Blattner FR, Cheng HL, Tucker PW, Mushinski JF. Mouse spleen and IgD-secreting plasmacytomas contain multiple IgD delta chain RNAs. Nature. 1982;296(5856):459-62.
[33] Perry RP, Kelley DE, Coleclough C, Seidman JG, Leder P, Tonegawa S, Matthyssens G, Weigert M. Transcription of mouse kappa chain genes: implications for allelic exclusion. Proc Natl Acad Sci U S A. 1980;77(4):1937-41.
[34] Tosi M, Young RA, Hagenbüchle O, Schibler U. Multiple polyadenylation sites in a mouse alpha-amylase gene. Nucleic Acids Res. 1981;9(10):2313-23.
[35] Sasavage NL, Smith M, Gillam S, Woychik RP, Rottman FM. Variation in the polyadenylylation site of bovine prolactin mRNA. Proc Natl Acad Sci U S A. 1982;79(2):223-7.
[36] Setzer DR, McGrogan M, Nunberg JH, Schimke RT. Size heterogeneity in the 3' end of dihydrofolate reductase messenger RNAs in mouse cells. Cell. 1980;22(2 Pt 2):361-70.
[37] Sehgal PB. How many human interferons are there? Interferon. 1982;4:1-22.
[38] Gerlinger P, Krust A, LeMeur M, Perrin F, Cochet M, Gannon F, Dupret D, Chambon P. Multiple initiation and polyadenylation sites for the chicken ovomucoid transcription unit. J Mol Biol. 1982;162(2):345-64.
[39] Content J, De Wit L, Tavernier J, Fiers W. Human fibroblast interferon RNA transcripts of different sizes in poly(I).poly(C) induced cells. Nucleic Acids Res. 1983;11(9):2627-38.
[40] Capetanaki YG, Ngai J, Flytzanis CN, Lazarides E. Tissue-specific expression of two mRNA species transcribed from a single vimentin gene. Cell. 1983;35(2 Pt 1):411-20.
[41] Lagace L, Chandra T, Woo SL, Means AR. Identification of multiple species of calmodulin messenger RNA using a full length complementary DNA. J Biol Chem. 1983;258(3):1684-8.
[42] Parnes JR, Robinson RR, Seidman JG. Multiple mRNA species with distinct 3' termini are transcribed from the beta 2-microglobulin gene. Nature. 1983 Mar 31-Apr 6;302(5907):449-52.
[43] Amara SG, Evans RM, Rosenfeld MG. Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites. Mol Cell Biol. 1984;4(10):2151-60.
[44] Chu ML, de Wet W, Bernard M, Ramirez F. Fine structural analysis of the human pro-alpha 1 (I) collagen gene. Promoter structure, AluI repeats, and polymorphic transcripts. J Biol Chem. 1985;260(4):2315-20.
[45] Chu ML, 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;260(7):4357-63.
[46] Zaret KS, Sherman F. DNA sequence required for efficient transcription termination in yeast. Cell. 1982;28(3):563-73.
[47] Salditt-Georgieff M, Darnell JE Jr. A precise termination site in the mouse beta-major globin transcription unit. Proc Natl Acad Sci U S A. 1984;81(7):2274.
[48] Rohrbaugh ML, Johnson JE 3rd, James MD, Hardison RC. Transcription unit of the rabbit beta 1 globin gene. Mol Cell Biol. 1985;5(1):147-60.
[49] Frayne EG, Leys EJ, Crouse GF, Hook AG, Kellems RE. Transcription of the mouse dihydrofolate reductase gene proceeds unabated through seven polyadenylation sites and terminates near a region of repeated DNA. Mol Cell Biol. 1984;4(12):2921-4.
[50] Proudfoot NJ, Brownlee GG. Sequence at the 3' end of globin mRNA shows homology with immunoglobulin light chain mRNA. Nature. 1974;252(5482):359-62.
[51] Ghazarian CG, Tarantul VZ. Eukaryotic genomes. M.: Izd-vo Mosk. un-ta, 1983. 268 p.
[52] Wickens M, Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984;226(4678):1045-51.
[53] Fitzgerald M, Shenk T. The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs. Cell. 1981;24(1):251-60.
[54] Montell C, Fisher EF, Caruthers MH, Berk AJ. Inhibition of RNA cleavage but not polyadenylation by a point mutation in mRNA 3' consensus sequence AAUAAA. Nature. 1983 Oct 13-19;305(5935):600-5.
[55] Orkin SH, Cheng TC, Antonarakis SE, Kazazian HH Jr. Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. EMBO J. 1985;4(2):453-6.
[56] Higgs DR, Goodbourn SE, Lamb J, Clegg JB, Weatherall DJ, Proudfoot NJ. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature. 1983 Nov 24-30;306(5941):398-400.
[57] Boardman M, Basi GS, Storti RV. Multiple polyadenylation sites in a Drosophila tropomyosin gene are used to generate functional mRNAs. Nucleic Acids Res. 1985;13(5):1763-76.
[58] Jung A, Sippel AE, Grez M, Schutz G. Exons encode functional and structural units of chicken lysozyme. Proc Natl Acad Sci U S A. 1980;77(10):5759-63.
[59] Mason PJ, Jones MB, Elkington JA, Williams JG. Polyadenylation of the Xenopus beta 1 globin mRNA at a downstream minor site in the absence of the major site and utilization of an AAUACA polyadenylation signal. EMBO J. 1985;4(1):205-11.
[60] McLauchlan J, Gaffney D, Whitton JL, Clements JB. The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3' termini. Nucleic Acids Res. 1985;13(4):1347-68.
[61] Manley JL, Yu H, Ryner L. RNA sequence containing hexanucleotide AAUAAA directs efficient mRNA polyadenylation in vitro. Mol Cell Biol. 1985;5(2):373-9.
[62] Birchmeier C, Schümperli D, Sconzo G, Birnstiel ML. 3' editing of mRNAs: sequence requirements and involvement of a 60-nucleotide RNA in maturation of histone mRNA precursors. Proc Natl Acad Sci U S A. 1984;81(4):1057-61.
[63] Stunnenberg HG, Birnstiel ML. Bioassay for components regulating eukaryotic gene expression: a chromosomal factor involved in the generation of histone mRNA 3' termini. Proc Natl Acad Sci U S A. 1982;79(20):6201-4.
[64] Mattaj IW. snRNAs from gene architecture to RNA processing. Trends Biochem Sci. 1984; 9(10):435-438.
[65] Turner P. Controlling roles for snurps. Nature. 1985 Jul 11-17;316(6024):105-6.
[66] Flavell AJ, Cowie A, Legon S, Kamen R. Multiple 5' terminal cap structures in late polyoma virus RNA. Cell. 1979;16(2):357-71.
[67] Baker CC, Ziff EB. Promoters and heterogeneous 5' termini of the messenger RNAs of adenovirus serotype 2. J Mol Biol. 1981;149(2):189-221.
[68] Dolan M, Dodgson JB, Engel JD. Analysis of the adult chicken beta-globin gene. Nucleotide sequence of the locus, microheterogeneity at the 5'-end of beta-globin mRNA, and aberrant nuclear RNA species. J Biol Chem. 1983;258(6):3983-90.
[69] Cowie A, Tyndall C, Kamen R. Sequences at the capped 5'-ends of polyoma virus late region mRNAs: an example of extreme terminal heterogeneity. Nucleic Acids Res. 1981;9(23):6305-22.
[70] Shatkin A. J. Introduction. Elucidating mechanism of eukaryotic genetic expression by studying animal viruses. Current topics in microbiology and immunology. Eds. W. Henle at al. New York etc : Springer-Verlag, 1981; 93:1-4.
[71] Lai EC, Roop DR, Tsai MJ, Woo SL, O'Malley BW. Heterogeneous initiation regions for transcription of the chicken ovomucoid gene. Nucleic Acids Res. 1982;10(18):5553-67.
[72] Selvanayagam CS, Tsai SY, Tsai MJ, Selvanayagam P, Saunders GF. Multiple origins of transcription for the human placental lactogen genes. J Biol Chem. 1984;259(23):14642-6.
[73] Field LJ, Philbrick WM, Howles PN, Dickinson DP, McGowan RA, Gross KW. Expression of tissue-specific Ren-1 and Ren-2 genes of mice: comparative analysis of 5'-proximal flanking regions. Mol Cell Biol. 1984;4(11):2321-31.
[74] Allan M, Lanyon WG, Paul J. Multiple origins of transcription in the 4.5 Kb upstream of the epsilon-globin gene. Cell. 1983;35(1):187-97.
[75] Grindlay GJ, Lanyon WG, Allan M, Paul J. Alternative sites of transcription initiation upstream of the canonical cap site in human gamma-globin and beta-globin genes. Nucleic Acids Res. 1984;12(4):1811-20.
[76] Carlson DP, Ross J. Human beta-globin promoter and coding sequences transcribed by RNA polymerase III. Cell. 1983;34(3):857-64.
[77] Carlson DP, Ross J. alpha-Amanitin-insensitive transcription of mouse beta major-globin 5'-flanking and structural gene sequences correlates with mRNA expression. Proc Natl Acad Sci U S A. 1984;81(24):7782-6.
[78] Manley JL, Colozzo MT. Synthesis in vitro of an exceptionally long RNA transcript promoted by an AluI sequence. Nature. 1982;300(5890):376-9.
[79] Winicov I., Weidner D. Transcription initiation in b-globin region from induced friend cell nuclei. 13th Int. congr. biochem. : Abstr. (Friday, August 30). Amsterdam, 1985:656.
[80] Selby MJ, Barta A, Baxter JD, Bell GI, Eberhardt NL. Analysis of a major human chorionic somatomammotropin gene. Evidence for two functional promoter elements. J Biol Chem. 1984;259(21):13131-8.
[81] Crossland LD, Rodermel SR, Bogorad L. Single gene for the large subunit of ribulosebisphosphate carboxylase in maize yields two differentially regulated mRNAs. Proc Natl Acad Sci U S A. 1984;81(13):4060-4.
[82] Reynolds GA, Goldstein JL, Brown MS. Multiple mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A reductase determined by multiple transcription initiation sites and intron splicing sites in the 5'-untranslated region. J Biol Chem. 1985;260(18):10369-77.
[83] Moon E, Kao TH, Wu R. Pea cytochrome oxidase subunit II gene has no intron and generates two mRNA transcripts with different 5'-termini. Nucleic Acids Res. 1985;13(9):3195-212.
[84] McGrogan M, Simonsen CC, Smouse DT, Farnham PJ, Schimke RT. Heterogeneity at the 5' termini of mouse dihydrofolate reductase mRNAs. Evidence for multiple promoter regions. J Biol Chem. 1985;260(4):2307-14.
[85] Masters JN, Attardi G. Discrete human dihydrofolate reductase gene transcripts present in polysomal RNA map with their 5' ends several hundred nucleotides upstream of the main mRNA start site. Mol Cell Biol. 1985;5(3):493-500.
[86] Schibler U, Hagenbüchle O, Wellauer PK, Pittet AC. Two promoters of different strengths control the transcription of the mouse alpha-amylase gene Amy-1a in the parotid gland and the liver. Cell. 1983;33(2):501-8.
[87] Nabeshima Y, Fujii-Kuriyama Y, Muramatsu M, Ogata K. Alternative transcription and two modes of splicing results in two myosin light chains from one gene. Nature. 1984 Mar 22-28;308(5957):333-8.