Biogenesis of a transforming gene

Beveren, Charles Van; Goddard, J. G.; Berns, Anton; Verma, Inder M.

doi:10.1007/bf00778748

Cited by 4 publications

(5 citation statements)

References 4 publications

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“…The sequence of restriction fragments was determined by the partial chemical degradation method (15,16 (22). In the accompanying paper, van Beveren et al (20) demonstrate that the sequence at the 5' end of the integrated Moloney MLV diverges completely from our 3' sequence at base 516 (our numbers) but matches it in the bases preceding and including 515. In their case, bases 516 and on represent cellular DNA; in our case these sequences are in the body of the virus.…”

Section: Methodssupporting

confidence: 49%

See 1 more Smart Citation

Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene.

Sutcliffe¹,

Shinnick²,

Verma³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

114

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We have determined the sequence of a cloned DNA fragment 1108 base pairs long which corresponds to the 3' end of the Moloney murine leukemia provirus. The clone was obtained as the primary product of reverse transcription and begins with the Moloney "strong stop" sequence, then extends towards the 5' end of the provirus. Our sequence: (i) proves that reverse transcriptase switches templates during minus strand synthesis; (ii) defines the limits of the 515-base-pair repeats which occupy both ends of the integrated provirus; (iii) shows that the structure of the proviral repeats has strong analogy to bacterial insertion sequences, indicating that the Moloney provirus is a transposon; (iv) identifies the putative promotor for genomic transcription within these repeats; (v) (MLV) (1) has long been the focus for biochemical and structural studies as a prototype for the mammalian RNA tumor viruses. Central to understanding the biology of retroviruses is the unambiguous assignment of genes to the RNA genome. In addition, because these viruses represent fragments of "selfish" nucleic acid (2) which can exist either free in a virion or associated with a cellular genome, the ends of the replicating molecule and its mode of replication are of particular interest.After infection, the virus-coded reverse transcriptase enzyme copies the Moloney virus single-stranded RNA genome into double-stranded DNA (3). Studies of reverse transcription in vitro indicate that DNA synthesis is initiated by the covalent elongation of the priming tRNA molecule which is bound near the 5' end of the RNA genome (4). Synthesis proceeds in a 5'-to-3' fashion, polymerizing deoxyribonucleotides complementary to the RNA genome such that the 5' end of the template is soon reached. The nascent single-stranded DNA molecule is then thought to migrate to the 3' end of the RNA template, where it may pair by virtue of complementary nucleotides with the string of approximately 60 bases immediately 5' to the poly(A) tail on that end of the genome (5). The nascent chain is then elongated, presumably continuously, to the 5' end of the template, producing a complete minus strand DNA copy of the virus genome. The mechanism for second-strand DNA synthesis and for producing a repeated end structure, thus We are studying the structure of proviral DNA cloned in bacterial vectors. Our initial attention has been drawn to the 3' end, where much of the molecular interest is. We choose to study the nucleotide sequences of cloned DNA fragments rather than that of whole viral RNA preparations because these RNA viruses have a low ratio of infectious virus to particle and the RNA is quite heterogeneous. Ultimately, the cloned DNA segments may be shown by transfection studies to harbor full biological activity, a feature not possible with RNA populations.We have investigated the molecular architecture of the product of the initial events in reverse transcription and have completely defined at the DNA sequence level the 5' end of the minus strand DNA. The sequence ex...

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Section: Methodssupporting

confidence: 49%

“…We have called them IRR and IRL for inverted repeat, right and left. The same repeating units are seen in the 5' long terminal repeat (20). Such repeats are reminiscent of the structures found in genetic elements called insertion sequences (23).…”

Section: Methodsmentioning

confidence: 75%

Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene.

Sutcliffe¹,

Shinnick²,

Verma³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

114

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“…As was the case for the 5' to 3' elongated DNA transcripts synthesized in vitro, ASV vDNA synthesized in vivo also contains only one DNA copy of the viral genomic terminal redundancy. This finding is consistent with those obtained for two retrovirus groups unrelated to ASV, spleen necrosis virus and Moloney murine leukemia-sarcoma virus (10,21,23,25,26). Cloned DNA was also sequenced through the tRNAtrP primer binding site.…”

Section: Downloaded Fromsupporting

confidence: 85%

Direct Proof of the 5′ to 3′ Transcriptional Jump During Reverse Transcription of the Avian Retrovirus Genome by DNA Sequencing

Omer

Parsons

Faras

1981

J Virol

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“…Many infected cells are haploid for viral genes, because they have acquired only a single provirus (5,6), but a portion of viral RNA is duplicated to form the LTR's found at the 5' and 3' end of each provirus (6,7). The LTR unit represents a fusion of sequences characteristic of the 3' end of viral RNA (U3), the R (11); the endogenous chicken provirus at the evl locus (19); spleen necrosis virus (SNV), an avian reticuloendotheliosis virus (10); Moloney strains of murine leukemia and murine sarcoma viruses (MLV, MSV) (8,9); and mouse mammary tumor virus (MMTV) (24). The nature of these domains is explained in the text and the legend to Fig.…”

Section: Reverse Transcription: Problems and Solutionsmentioning

confidence: 99%

“…j-- 21 MAY 1982 sequence, and sequences that are characteristic of the 5' end of viral RNA (U5), in the order 5'-U3-R-U5-3' (Figs. 1 and 2); and it is terminated by short sequences forming inverted and often imperfect repeats (8)(9)(10)(11)(12) (Table I and Fig. 2).…”

Section: Reverse Transcription: Problems and Solutionsmentioning

confidence: 99%

Form and Function of Retroviral Proviruses

Varmus

1982

Science

591

262

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Retroviruses have proved to be useful reagents for studying genetic and epigenetic (such as regulatory) changes in eukaryotic cells, for assessing functional and structural relationships between transposable genetic elements, for inducing insertional mutations, including some important in oncogenesis, and for transporting genes into eukaryotic cells, either after natural transduction of putative cellular oncogenes or after experimental construction of recombinant viruses. Many of these properties of retroviruses depend on their capacity to establish a DNA (proviral) form of their RNA genomes as a stable component of host chromosomes, in either somatic or germinal cells.

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Biogenesis of a transforming gene

Cited by 4 publications

References 4 publications

Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene.

Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene.

Direct Proof of the 5′ to 3′ Transcriptional Jump During Reverse Transcription of the Avian Retrovirus Genome by DNA Sequencing

Form and Function of Retroviral Proviruses

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