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Titolo:
A cis-acting element in the 3 '-untranslated region of human TNF-alpha mRNA renders splicing dependent on the activation of protein kinase PKR
Autore:
Osman, F; Jarrous, N; Ben-Asouli, Y; Kaempfer, R;
Indirizzi:
Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 -91120 Jerusalem, Israel
Titolo Testata:
GENES & DEVELOPMENT
fascicolo: 24, volume: 13, anno: 1999,
pagine: 3280 - 3293
SICI:
0890-9369(199912)13:24<3280:ACEIT3>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOUBLE-STRANDED-RNA; PRE-MESSENGER-RNA; INTERLEUKIN-2 GENE-EXPRESSION; NECROSIS-FACTOR GENES; BINDING DOMAIN; HUMAN-CELLS; TRANSCRIPTIONAL ACTIVATION; MALIGNANT TRANSFORMATION; EUKARYOTIC TRANSLATION; PRECURSOR TRANSCRIPTS;
Keywords:
splicing; tumor necrosis factor; cis-acting RNA element; 3 '-untranslated region; protein kinase PKR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Kaempfer, R Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 alem, Israel
Citazione:
F. Osman et al., "A cis-acting element in the 3 '-untranslated region of human TNF-alpha mRNA renders splicing dependent on the activation of protein kinase PKR", GENE DEV, 13(24), 1999, pp. 3280-3293

Abstract

We report a role for the 3'-untranslated region in control of mRNA splicing and show that human TNF-alpha 3' UTR harbors a cis-acting element that renders splicing of precursor transcripts dependent on activation of PKR, theRNA-activated protein kinase that phosphorylates eukaryotic initiation factor 2 (eIF2). When this element, designated 2-APRE, is present, splicing becomes sensitive to inhibition by the PKR inhibitor e-aminopurine, or by coexpression of transdominant-negative mutant PKR. Our results reveal that activation of PKR is required for splicing of mRNA when precursor transcripts contain the 2-APRE and that increased expression of wild-type PKR enhances their splicing efficiency. Thus, PKR responds as trans-acting factor to the2-APRE. 2-APRE RNA forms a stable, 17-bp stem-loop structure and strongly activates PKR ill vitro, inducing eIF2 alpha phosphorylation. Despite its ability to activate PKR during splicing, the 2-APRE within the 3' UTR does not affect translation efficiency of the resulting TNF-alpha mRNA in transfected cells. PKR and the 3' UTR thus interact during mRNA splicing to confera novel type of regulation on expression of the TNF-alpha gene.

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Documento generato il 21/09/20 alle ore 02:52:36