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C Vanhée-Brossollet

Publications and source records attributed to C Vanhée-Brossollet.

4 recordsLinked to original sources

Natural antisense transcripts are detected in different cell lines and tissues of cats infected with feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) is a lentivirus inducing an AIDS-like disease in cats, thus providing an interesting model for AIDS study. FIV and HIV-1 possess a similar genomic arrangement of structural and non-structural genes, whose expression is regulated by related genetic mechanisms. On the DNA strand complementary to the HIV-1 envelope messenger, an open reading frame (ORF) has been identified which encompasses the Rev Responsive Element (RRE), a cis-acting element critical to HIV gene expression. This ORF was highly conserved among HIV-1 isolates and had the potential to encode a hydrophobic protein. A corresponding antisense transcript was detected in cells infected with HIV-1, and appeared to encode an antisense protein. In the present study, we have identified a well-conserved antisense ORF, also coincident with the RRE region, in the genome of 21 FIV isolates. The predicted protein, 103 amino acids in length, is highly hydrophobic, as is the case for that of HIV-1. In addition, we have shown that a corresponding transcript, complementary to the transmembrane sequence of the FIV envelope gene, was produced in different cellular and viral contexts, that is, ex vivo and in vivo in FIV infected cell lines and tissues of infected cats, respectively. Expression of antisense transcripts might therefore be of general importance in the natural history of retroviruses.

Amino Acid Sequence↗

Do natural antisense transcripts make sense in eukaryotes?

The existence of naturally occurring antisense RNAs has been illustrated, in eukaryotes, by an increasing number of reports. The following review presents the major findings in this field, with a special focus on the regulation of gene expression exerted by endogenous complementary transcripts. A large variety of eukaryotic organisms, contains antisense transcripts. Moreover, the great diversity of genetic loci encoding overlapping sense and antisense RNAs suggests that such transcripts may be involved in numerous biological functions, such as control of development, adaptative response. viral infection. The regulation of gene expression by endogenous antisense RNAs seems of general importance in eukaryotes as already established in prokaryotes: it is likely to be involved in the control of various biological functions and to play a role in the development of pathological situations. Several experimental evidences for coupled, balanced or unbalanced expression of sense and antisense RNAs suggest that antisense transcripts may govern the expression of their sense counterparts. Furthermore, documented examples indicate that this control may be exerted at many levels of gene expression (transcription, maturation, transport, stability and translation). This review also addresses the underlying molecular mechanisms of antisense regulation and presents the current mechanistic hypotheses.

Animals↗

Regulation of p56(lck) messenger turnover upon T cell activation: involvement of the 3' untranslated region in stability as determined in cell-free extracts.

Full activation of T lymphocytes transiently downregulates the steady state level of the tyrosine kinase p56(lck) mRNA. Here, we show that a decrease in messenger stability is involved in this downmodulation followed thereafter by a rapid and marked increase in mRNA half-life. In order to facilitate the study of p56(lck) messenger stability, an in vitro mRNA decay assay was developed and used to determine whether the 451 nucleotide long 3' untranslated region (3'UTR) of the messenger is implicated in the regulation of mRNA stability. Indeed, deletion of most of the 3'UTR led to a substantial increase in transcript half-life whereas deletion of a limited 3' portion did not, thus showing that the 146 nucleotides located in 5' of the 3'UTR contain destabilizing elements. Furthermore, the stability of both truncated transcripts was still modulated upon activation, thereby suggesting that the activation-responsive elements are located in a region distinct from the 3'UTR.

Cell-Free System↗

A natural antisense RNA derived from the HIV-1 env gene encodes a protein which is recognized by circulating antibodies of HIV+ individuals.

A naturally occurring antisense RNA, transcribed in the opposite direction and complementary to the envelope transcript, was identified in various cell lines chronically infected with HIV-1. In T cells, the antisense transcript is constitutively expressed and enhanced by activation with phorbol myristate acetate. The open reading frame corresponding to the antisense transcript, when expressed in vitro, encodes a protein with an apparent molecular mass of 19 kDa. Antibodies against this protein have been detected in several sera of HIV+ individuals and not in any of the noninfected control sera. These results indicate, for the first time, that expression of an antisense open reading frame most likely accompanies the HIV infection cycle in humans.

Base Sequence↗