Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Function of the human T-cell leukemia virus Rex response element in viral RNA processing.
Diss Abstr Int [B]; 53(12):6110 1993. Unique Identifier : AIDSLINE ICDB/94696128 Ahmed YF; Duke Univ.
Abstract:
The type I human T cell leukemia virus (HTLV-I) is the etiologic agent of an aggressive malignancy of human CD4+ T lymphocytes known as adult T cell leukemia. In addition to the gag, pol and env genes present in all replication-competent retroviruses, HTLV contains two additional regulatory genes tax and rex. The HTLV-I Rex protein functions at a post-transcriptional level to augment the cytoplasmic expression of the unspliced and singly spliced viral mRNA species that encode the gag, pol, and env gene products. The action of Rex requires a large cis-regulatory RNA sequence present in all viral transcripts termed the Rex response element (RexRE). Using a mutational analysis of the RexRE, we delineate 7 nucleotides of the 255 nucleotide element that appear to be critical contact points for the Rex protein. These nucleotides are located directly on opposing sides of a stem-like subregion within the element that is predicted by computer modeling. Substitution mutations within this subregion decrease the binding of Rex to its response element and thereby decrease the in vivo Rex response. Rex action requires both the overall secondary structure intrinsic to the RexRE, and these seven specific nucleotides in one stem-like subregion. In addition to regulating structural gene expression, the RexRE plays a critical role in the polyadenylation of all HTLV-I mRNA transcripts in a manner that is independent of Rex. Specifically, folding of the RexRE serves to spatially juxtapose the distantly separated AAUAAA hexamer sequence and the GU-rich element located downstream of the cleavage site thereby allowing 3' processing to occur. Studies employing an in vitro assay of polyadenylation have revealed that folding of the RexRE is essential for the cooperative and stable binding of two enriched nuclear factors at the upstream hexamer sequence and the downstream GU-rich element which in turn commits this viral poly A site to 3' processing. Thus using a twist on the standard tricks utilized by retroviruses, HTLV-I employs a single cis-acting highly structured RNA element to deal with two problems specific to retroviral RNA processing. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD93-12365)
Keywords: Gene Products, rex/*GENETICS Gene Products, tax/*GENETICS Human Leukemia, T-Cell/*GENETICS RNA Splicing RNA, Messenger/GENETICS RNA, Viral/GENETICS Transcription, Genetic THESIS
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
