Structure of Moloney murine leukemia viral DNA: nucleotide sequence of the 5' long terminal repeat and adjacent cellular sequences.

Abstract

Some unintegrated and all integrated forms of murine leukemia viral DNA contain long terminal repeats (LT s). The entire nucleotide sequence of the LTR and adjacent cellular sequences at the 5' end of a cloned integrated proviral DNA obtained from BALB/Mo mouse has been determined. It was compared to the nucleotide sequence of the LTR at the 3' end. The results indicate: (i) a direct 517-nucleotide repeat at the 5' and 3' termini; (ii) 145 nucleotides out of 517 nucleotides represent sequences between the 5'-CAP nucleotide and 3' end of the primer tRNA (strong-stop DNA); (ifi) an li-nucleotide inverted repeat is present at the ends of the 5'-LTR and a total of 17 out of21 nucleotides at the termini are inverted repeats; (iv) sequences CAATAAAAG (at positions -24 to -31) and CAATAAAC (at positions +46 to +53) resembling the hypothetical DNA-dependent RNA polymerase II promoter site can be identified in the 5'-LTR; (v) the sequence GAAA appears to be repeated on both sides of the junction of viral and cellular sequences; and (vi) in analogy with the bacterial transposons, the presence of an inverted reat seuence at the termini of 5'-LTR suggests that M-MLV also has the integration properties of a transposon.

Endogenous murine leukemia proviral long terminal repeats contain a unique 190-base-pair insert.

“…LTRs contain important regulatory signals for the promotion, initiation, and processing of viral mRNAs and may play a role in the integration of proviral DNA into the host chromosome (3). Furthermore, nucleotide sequence analyses show that LTRs possess structural features characteristic of transposable elements found in bacteria, yeast, and Drosophila (4)(5)(6)(7)(8)(9)(10)(11).In several vertebrate species, DNA copies of type C retroviruses have been identified as genetically stable integral components of chromosomal DNA (12). Such endogenous proviruses have been shown to be vertically transmitted, can be mapped to specific chromosomal loci, and, in some cases, may be expressed as infectious retroviruses (12).…”

Possible DNA-RNA tumor virus interaction in human lymphomas: expression of retroviral proteins in Ramos lymphoma lines is enhanced after conversion with Epstein-Barr virus.

“…Our rationale is based on the mechanism of MuLV activation of cellular onc genes, which may be relevant. The 5' long-terminal repeats of the MuLV provirus have been shown to contain a hypothetical promoter site for transcription (21). Hayward et at.…”

Identification of a RNA polymerase II initiation site in the long terminal repeat of Moloney murine leukemia viral DNA.

“…It thus appears plausible that proviral DNA might contain its own promoter for initiation of transcription, although the possibility that the transcription of an integrated provirus is under the control of closely juxtaposed cellular promoters cannot be excluded. Structural analysis of the long terminal repeat (LTR) from several murine and avian retroviruses shows a sequence similar to a Hogness-Goldberg (T-A-T-A) box, upstream from the 5'-cap nucleotide (12)(13)(14)(15)(16)(17)(18). The Rous sarcoma virus LTR contains an in vitro RNA polymerase II initiation site 23 base pairs (bp) downstream from a T-A-T-A-box-like sequence (18).…”

“…The complete nucleotide sequences of the 5' LTR of an integrated Moloney murine leukemia virus (M-MuLV) DNA and of an LTR of an unintegrated form of M-MuLV DNA have been determined (ref. 13; unpublished results); the sequences include the 5'-cap site of viral RNA and two possible T-A-T-A-like boxes (13). One of the T-A-T-A-like sequences is located immediately to the right of the Sac I site, at position -25 to -31 ofthe LTR (Sac-T-A-T-A-like), and is likely to be part of the initiation site used for viral RNA synthesis.…”