Abstract
Since the determination of the informational molecule deoxyribonucleic acid (DNA) structure by Watson and Crick in 1953, molecular biology had a fantastic development that culminated in recent times with the possibility of determining the nucleotide sequence of whole information content of various organisms. The discovery of interrupted (split) genes configuration and the discrimination of sequences called exons and introns were a key step to understanding the architecture, functioning and regulation of gene expression. This is the first article of a series that aims to survey the fundamental experiments of the discovery of various introns types. In this initial article, we describe the antecedents and the discovery of interrupted genes of pre-mRNAs that accounted for the initial mark of the description of this type of gene organization. The rescue of the history of interrupted genes discovery and description of the processes and methods involved has its importance in the origin of a wide source of techniques and analysis used in the studies of gene regulation mechanisms nowadays which has profound impact in various human activities.
References
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Berget SM, Moore C, Sharp PA. Spliced segments at the 5’ terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. USA, 1977, n(74): 3171-3175.
Breathnach R, Mandel JL, Chambon P. Ovalbumin gene is split in chicken DNA. Nature, 1977, n(270): 314-319.
Chow LT, Gelinas RE, Broker TR, Roberts RJ. An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell, 1977, n(12): 1-8.
Cech TR, Rio DC. (1979). Localization of transcribed regions on extrachromosomal ribosomal RNA genes of Tetrahymena thermophila by R-loop mapping. Proc. Natl. Acad. Sci. USA, 1979, n(76): 5051-5055.
Crick F. Split genes and RNA splicing. Science, 1979, n(204): 264-271.
Darnell JE. The origin of mRNA and the structure of the mammalian chromosome. Harvey Lect, 1973, n(69): 1-47.
______, Wall R, Tushinski RJ. An adenylic acid-rich sequence in messenger RNA of HeLa cells and its possible relationship to reiterated sites in DNA. Proc. Natl. Acad. Sci. USA, 1971, n(68): 1321-1325.
Din N, Engberg J. Extrachromosomal ribosomal RNA genes in Tetrahymena: structure and evolution. J. Mol. Biol. 1979, n(134): 555-574.
Din N, Engberg J, Kaffenberger W, Eckert WA. The intervening sequence in the 26S rRNA coding region of T. thermophila is transcribed within the largest stable precursor for rRNA. Cell, 1979, n(18): 525-532.
Dugaiczyk A et al. The natural ovalbumin gene contains seven intervening sequences. Nature, 1978, n(274): 328-333.
Edmonds M, Vaughan Jr. MH, Nakazato H. Polyadenylic acid sequences in the heterogeneous nuclear RNA and rapidly-labeled polyribosomal RNA of HeLa cells: possible evidence for a precursor relationship. Proc. Natl. Acad. Sci. USA, 1971, n(68): 1336-1340.
Furuichi Y, Morgan M, Muthukrishnan S, Shatkin AJ. Reovirus messenger RNA contains a methylated, blocked 5’-terminal structure: m-7G(5’) ppp(5’) G-MpCp. Proc. Natl. Acad. Sci. USA, 1975, n(72): 362-366.
Garapin AC et al. Electron microscopy and restriction enzyme mapping reveal additional intervening sequences in the chicken ovalbumin split gene. Cell, 1978, n(14): 629-639.
Garapin AC et al. Isolation by molecular cloning of a fragment in the split ovalbumin gene. Nature, 1978b, n(273): 349-354.
Gelinas RE, Roberts RJ. One predominant 5’-undecanucleotide in adenovirus 2 late messenger RNAs. Cell, 1977, n(11): 533-544.
Gilbert W. Why genes in pieces? Nature, 1978, n(271): 501.
Goodman HM, Olson MV, Hall BD. Nucleotide sequence of a mutant eukaryotic gene: the yeast tyrosine-inserting ochre suppressor SUP4-o. Proc. Natl. Acad. Sci. USA, 1977, n(74): 5453-5457.
Humphries P et al. Molecular cloning of extensive sequences of the in vitro synthesized chicken ovalbumin structural gene. Nucleic Acids Res, 1977, n(4): 2389-2406.
Jeffreys AJ, Flavell RA. The rabbit beta-globin gene contains a large insert in the coding sequence. Cell, 1977, n(12): 1097-1108.
Lee SY, Mendecki J, Brawerman G. A polynucleotide segment rich in adenylic acid in the rapidly-labeled polyribosomal RNA component of mouse sarcoma 180 ascites cells. Proc. Natl. Acad. Sci. USA, 1971, n(68): 1331-1335.
Lewin B. Gene Expression, 1980, v(2), 2nd. edn (New York, John Wiley & Sons).
______. (1982). Gene Expression, 1982, v(1), 6th. edn (New York, John Wiley & Sons).
Mandel JL et al. Organization of coding and intervening sequences in the chicken ovalbumin split gene. Cell, 1978, n(14): 641-653.
Moss B, Koczot F. Sequence of methylated nucleotides at the 5’-terminus of adenovirus-specific RNA. J Virol, 1976, n(17): 385-392.
O’Hare K, Breathnach R, Benoist C, Chambon P. No more than seven interruptions in the ovalbumin gene: comparison of genomic and double-stranded cDNA sequences. Nucleic Acids Res., 1979, n(7): 321-334.
Philipson L, Wall R, Glickman G, Darnell JE. Addition of polyadenylate sequences to virus-specific RNA during adenovirus replication. Proc. Natl. Acad. Sci. USA, 1971, n(68): 2806-2809.
Roop DR et al. Transcription of structural and intervening sequences in the ovalbumin gene and identification of potential ovalbumin mRNA precursors. Cell, 1978, n(15): 671-685.
Rottman F, Shatkin AJ, Perry RP. Sequences containing methylated nucleotides at the 5’ termini of messenger RNAs: possible implications for processing. Cell, 1974, n(3): 197-199.
Thomas M, White RL, Davis RW. Hybridization of RNA to double-stranded DNA: formation of R-loops. Proc. Nat.l Acad. Sci. USA, 1976, n(73): 2294-2298.
Tilghman SM et al. The intervening sequence of a mouse beta-globin gene is transcribed within the 15S beta-globin mRNA precursor. Proc. Natl. Acad. Sci. USA, 1978a, n(75): 1309-1313.
Tilghman SM et al. Intervening sequence of DNA identified in the structural portion of a mouse beta-globin gene. Proc. Natl. Acad. Sci. USA, 1978b, n(75): 725-729.
Tonegawa S et al. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc. Natl. Acad. Sci. USA, 1978, n(75): 1485-1489.
Valenzuela P et al. Structure of yeast phenylalaninetRNA genes: an intervening DNA segment within the region coding for the tRNA. Proc. Natl. Acad. Sci. USA, 1978, n(75): 190-194.
Wei CM, Moss B. Methylation of newly synthesized viral messenger RNA by an enzyme in vaccinia virus. Proc. Natl. Acad. Sci. USA, 1974, n(68): 1336-1340.
Wild MA, Gall JG. An intervening sequence in the gene coding for 25S ribosomal RNA of Tetrahymena pigmentosa. Cell, 1979, n(16): 565-573.
Berget SM, Moore C, Sharp PA. Spliced segments at the 5’ terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. USA, 1977, n(74): 3171-3175.
Breathnach R, Mandel JL, Chambon P. Ovalbumin gene is split in chicken DNA. Nature, 1977, n(270): 314-319.
Chow LT, Gelinas RE, Broker TR, Roberts RJ. An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell, 1977, n(12): 1-8.
Cech TR, Rio DC. (1979). Localization of transcribed regions on extrachromosomal ribosomal RNA genes of Tetrahymena thermophila by R-loop mapping. Proc. Natl. Acad. Sci. USA, 1979, n(76): 5051-5055.
Crick F. Split genes and RNA splicing. Science, 1979, n(204): 264-271.
Darnell JE. The origin of mRNA and the structure of the mammalian chromosome. Harvey Lect, 1973, n(69): 1-47.
______, Wall R, Tushinski RJ. An adenylic acid-rich sequence in messenger RNA of HeLa cells and its possible relationship to reiterated sites in DNA. Proc. Natl. Acad. Sci. USA, 1971, n(68): 1321-1325.
Din N, Engberg J. Extrachromosomal ribosomal RNA genes in Tetrahymena: structure and evolution. J. Mol. Biol. 1979, n(134): 555-574.
Din N, Engberg J, Kaffenberger W, Eckert WA. The intervening sequence in the 26S rRNA coding region of T. thermophila is transcribed within the largest stable precursor for rRNA. Cell, 1979, n(18): 525-532.
Dugaiczyk A et al. The natural ovalbumin gene contains seven intervening sequences. Nature, 1978, n(274): 328-333.
Edmonds M, Vaughan Jr. MH, Nakazato H. Polyadenylic acid sequences in the heterogeneous nuclear RNA and rapidly-labeled polyribosomal RNA of HeLa cells: possible evidence for a precursor relationship. Proc. Natl. Acad. Sci. USA, 1971, n(68): 1336-1340.
Furuichi Y, Morgan M, Muthukrishnan S, Shatkin AJ. Reovirus messenger RNA contains a methylated, blocked 5’-terminal structure: m-7G(5’) ppp(5’) G-MpCp. Proc. Natl. Acad. Sci. USA, 1975, n(72): 362-366.
Garapin AC et al. Electron microscopy and restriction enzyme mapping reveal additional intervening sequences in the chicken ovalbumin split gene. Cell, 1978, n(14): 629-639.
Garapin AC et al. Isolation by molecular cloning of a fragment in the split ovalbumin gene. Nature, 1978b, n(273): 349-354.
Gelinas RE, Roberts RJ. One predominant 5’-undecanucleotide in adenovirus 2 late messenger RNAs. Cell, 1977, n(11): 533-544.
Gilbert W. Why genes in pieces? Nature, 1978, n(271): 501.
Goodman HM, Olson MV, Hall BD. Nucleotide sequence of a mutant eukaryotic gene: the yeast tyrosine-inserting ochre suppressor SUP4-o. Proc. Natl. Acad. Sci. USA, 1977, n(74): 5453-5457.
Humphries P et al. Molecular cloning of extensive sequences of the in vitro synthesized chicken ovalbumin structural gene. Nucleic Acids Res, 1977, n(4): 2389-2406.
Jeffreys AJ, Flavell RA. The rabbit beta-globin gene contains a large insert in the coding sequence. Cell, 1977, n(12): 1097-1108.
Lee SY, Mendecki J, Brawerman G. A polynucleotide segment rich in adenylic acid in the rapidly-labeled polyribosomal RNA component of mouse sarcoma 180 ascites cells. Proc. Natl. Acad. Sci. USA, 1971, n(68): 1331-1335.
Lewin B. Gene Expression, 1980, v(2), 2nd. edn (New York, John Wiley & Sons).
______. (1982). Gene Expression, 1982, v(1), 6th. edn (New York, John Wiley & Sons).
Mandel JL et al. Organization of coding and intervening sequences in the chicken ovalbumin split gene. Cell, 1978, n(14): 641-653.
Moss B, Koczot F. Sequence of methylated nucleotides at the 5’-terminus of adenovirus-specific RNA. J Virol, 1976, n(17): 385-392.
O’Hare K, Breathnach R, Benoist C, Chambon P. No more than seven interruptions in the ovalbumin gene: comparison of genomic and double-stranded cDNA sequences. Nucleic Acids Res., 1979, n(7): 321-334.
Philipson L, Wall R, Glickman G, Darnell JE. Addition of polyadenylate sequences to virus-specific RNA during adenovirus replication. Proc. Natl. Acad. Sci. USA, 1971, n(68): 2806-2809.
Roop DR et al. Transcription of structural and intervening sequences in the ovalbumin gene and identification of potential ovalbumin mRNA precursors. Cell, 1978, n(15): 671-685.
Rottman F, Shatkin AJ, Perry RP. Sequences containing methylated nucleotides at the 5’ termini of messenger RNAs: possible implications for processing. Cell, 1974, n(3): 197-199.
Thomas M, White RL, Davis RW. Hybridization of RNA to double-stranded DNA: formation of R-loops. Proc. Nat.l Acad. Sci. USA, 1976, n(73): 2294-2298.
Tilghman SM et al. The intervening sequence of a mouse beta-globin gene is transcribed within the 15S beta-globin mRNA precursor. Proc. Natl. Acad. Sci. USA, 1978a, n(75): 1309-1313.
Tilghman SM et al. Intervening sequence of DNA identified in the structural portion of a mouse beta-globin gene. Proc. Natl. Acad. Sci. USA, 1978b, n(75): 725-729.
Tonegawa S et al. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc. Natl. Acad. Sci. USA, 1978, n(75): 1485-1489.
Valenzuela P et al. Structure of yeast phenylalaninetRNA genes: an intervening DNA segment within the region coding for the tRNA. Proc. Natl. Acad. Sci. USA, 1978, n(75): 190-194.
Wei CM, Moss B. Methylation of newly synthesized viral messenger RNA by an enzyme in vaccinia virus. Proc. Natl. Acad. Sci. USA, 1974, n(68): 1336-1340.
Wild MA, Gall JG. An intervening sequence in the gene coding for 25S ribosomal RNA of Tetrahymena pigmentosa. Cell, 1979, n(16): 565-573.
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