Bovine leukemia virus: unique structural features of its long terminal repeats and its evolutionary relationship to human T-cell leukemia virus.

Sagata, Noriyuki; Yasunaga, Teruo; Ogawa, Yoshiaki; Tsuzuku-Kawamura, Junko; Ikawa, Yoji

doi:10.1073/pnas.81.15.4741

Cited by 56 publications

(43 citation statements)

References 44 publications

(49 reference statements)

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“…In this regard, the extraordinarily long R regions within the LTRs of both HTLV-II and bovine leukemia virus (BLV) also form predicted stem-loop structures, a finding that distinguishes this family of retroviruses from all others (Sagata et al 1984;Kim et al, unpubl.). Although Rex responsiveness and polyadenylation can be clearly segregated (Hanly et al 1989), we have found that deletion of the major stem within the RexRE abolishes not only Rex responsiveness but also polyadenylation (Y. Ahmed, G. Gilmartin, S. Hanly, J. Nevins, and W. Greene, unpubl.).…”

Section: Discussionmentioning

confidence: 99%

Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action.

Ahmed¹,

Hanly²,

Malim³

et al. 1990

Genes Dev.

110

103

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The ability of the Rex protein of the type I human T-cell leukemia virus (HTLV-I) to regulate expression of the retroviral gag and env structural genes post-transcriptionally is critically dependent on the presence of a Rex response element (RexRE). This c/s-regulatory sequence is located within the retroviral 3' long terminal repeat and coincides with a predicted, highly stable RNA stem-loop structure. Rex action requires both the overall secondary structure intrinsic to the RexRE and specific sequences from one small subregion of this large structure. This small subregion likely forms a protein-binding site for Rex or a cellular RNA-binding factor. Whereas Rex can functionally replace the Rev protein of the type 1 human immunodeficiency virus (HIV-I} through its interaction with the analogous Rev response element (RevRE), distinct subregions of this HIV-1 RNA element mediate the responses to Rex and Rev. Strikingly, Rex acts as a dominant repressor of Rev action, following the deletion of the Rex responsive subregion of the RevRE. Similarly, Rev inhibits Rex function in a dominant manner when the Rev responsive subregion of the RevRE is deleted. Together, these findings suggest that Rex and Rev not only interact with their respective RNA response elements but also may either form mixed inactive multimers or interact with a common cellular factorIs). If binding of a common host protein is involved, this factor likely plays a central role either in spliceosome assembly or nuclear RNA transport.

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Section: Discussionmentioning

confidence: 99%

Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action.

Ahmed¹,

Hanly²,

Malim³

et al. 1990

Genes Dev.

110

103

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show abstract

“…Although in the vast majority of mRNAs the site at which poly(A) is added in vivo has always been found to be only 10 to 30 nucleotides downstream from an AAUAAA signal (4), recent data raise the possibility that this may not always be so. The distances between the apparent AAUAAA signals and the polyadenylation sites in human T-cell leukemia viruses I (35) and 11 (36) and bovine leukemia virus (34) RNAs are all over 200 nucleotides. Whether the mechanism by which these RNAs become poly(A)+ is directly related to the mechanism suggested by our in vitro findings remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

RNA sequence containing hexanucleotide AAUAAA directs efficient mRNA polyadenylation in vitro.

Manley¹,

Yu²,

Ryner³

1985

Mol. Cell. Biol.

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To determine whether a specific nucleotide sequence is required to direct polyadenylation of a simian virus 40 early pre-mRNA in a soluble HeLa whole-cell lysate, we constructed a series of rearranged and deleted DNA templates, transcribed them in vitro, and determined whether the resultant RNAs could be polyadenylated when incubated in whole-cell lysate. When a 237-base-pair DNA fragment encoding the 3' end of the simian virus 40 early pre-mRNA was transferred to recombinant plasmids encoding RNAs that were not substrates for polyadenylation, the resultant RNAs could now be polyadenylated efficiently. In one case, the chimeric RNA was polyadenylated even more efficiently than was the original simian virus 40 early transcript. Analysis of the RNAs produced from the deletion mutant templates revealed that only RNAs containing at least one copy of the AAUAAA sequence situated near the 3' end and implicated in 3'-end formation and polyadenylation in vivo could be polyadenylated in vitro. Surprisingly, this sequence directed polyadenylation of pre-mRNAs not only when near the RNA 3' end, i.e., 50 nucleotides or less away, but also when the 3' end was situated over 400 nucleotides downstream. Thus, our results show that a polyadenylic acid polymerase activity in HeLa lysates can recognize a specific nucleotide sequence in pre-mRNA and then, in the absence of the nucleolytic cleavage that presumably occurs in vivo, locate the RNA 3' end and use it as a primer for polyadenylic acid synthesis.

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“…In this regard; several groups have previously noted the exceptionally long R regions present in RNA tran scripts of HTLV-I, HTLV-II, and the related bovine leu kemia virus. It has also been proposed that these R re gions may be looped out (Sagata et al 1984;Sodroski et al 1984b), thereby approximating the two distantly sep arated sequence elements required for efficient cleavage and polyadenylation of the primary viral mRNA tran scripts (McDevitt et al 1984;Sodofsky et al 1985; for review, see Bimstiel et al 1985;Gil and Proudfoot 1987). Specifically, looping out of the R region would position the 3' GU boxes in U5 in correct spatial orientation with the AAUAAA motif present in US (see Fig.…”

Section: Htlv-i Rexre Corresponds To a Putative Rna Stem-loop Structurementioning

confidence: 99%

Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements.

Hanly¹,

Rimsky²,

Malim³

et al. 1989

Genes Dev.

183

142

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Bovine leukemia virus: unique structural features of its long terminal repeats and its evolutionary relationship to human T-cell leukemia virus.

Abstract: The nucleotide sequence of the long terminal repeat (LTR) of bovine leukemia virus, a unique oncogenic retrovirus of cattle, was determined. The LTR consisted of 530 base pairs (bp) with an inverted repeat of 6 bp at its 5' and 3'

Cited by 56 publications

References 44 publications

Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action.

Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action.

RNA sequence containing hexanucleotide AAUAAA directs efficient mRNA polyadenylation in vitro.

Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements.

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