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TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis

The transactivating response (TAR) RNA-binding protein (TRBP) has been identified as a double-stranded RNA (dsRNA)-binding protein, which associates with a stem-loop region known as the TAR element in human immunodeficiency virus-1 (HIV-1). However, TRBP is also known to be an enhancer of RNA silenc...

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Autores principales: Komori, Chiaki, Takahashi, Tomoko, Nakano, Yuko, Ui-Tei, Kumiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055394/
https://www.ncbi.nlm.nih.gov/pubmed/32051109
http://dx.doi.org/10.1242/bio.050435
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author Komori, Chiaki
Takahashi, Tomoko
Nakano, Yuko
Ui-Tei, Kumiko
author_facet Komori, Chiaki
Takahashi, Tomoko
Nakano, Yuko
Ui-Tei, Kumiko
author_sort Komori, Chiaki
collection PubMed
description The transactivating response (TAR) RNA-binding protein (TRBP) has been identified as a double-stranded RNA (dsRNA)-binding protein, which associates with a stem-loop region known as the TAR element in human immunodeficiency virus-1 (HIV-1). However, TRBP is also known to be an enhancer of RNA silencing, interacting with Dicer, an enzyme that belongs to the RNase III family. Dicer cleaves long dsRNA into small dsRNA fragments called small interfering RNA or microRNA (miRNA) to mediate RNA silencing. During HIV-1 infection, TAR RNA-mediated translation is suppressed by the secondary structure of 5′UTR TAR RNA. However, TRBP binding to TAR RNA relieves its inhibitory action of translation and Dicer processes HIV-1 TAR RNA to generate TAR miRNA. However, whether the interaction between TRBP and Dicer is necessary for TAR RNA translation or TAR miRNA processing remains unclear. In this study, we constructed TRBP mutants that were unable to interact with Dicer by introducing mutations into amino acid residues necessary for the interaction. Furthermore, we established cell lines expressing such TRBP mutants. Then, we revealed that the TRBP–Dicer interaction is essential for both the TAR-containing RNA translation and the TAR miRNA processing in HIV-1.
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spelling pubmed-70553942020-03-04 TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis Komori, Chiaki Takahashi, Tomoko Nakano, Yuko Ui-Tei, Kumiko Biol Open Research Article The transactivating response (TAR) RNA-binding protein (TRBP) has been identified as a double-stranded RNA (dsRNA)-binding protein, which associates with a stem-loop region known as the TAR element in human immunodeficiency virus-1 (HIV-1). However, TRBP is also known to be an enhancer of RNA silencing, interacting with Dicer, an enzyme that belongs to the RNase III family. Dicer cleaves long dsRNA into small dsRNA fragments called small interfering RNA or microRNA (miRNA) to mediate RNA silencing. During HIV-1 infection, TAR RNA-mediated translation is suppressed by the secondary structure of 5′UTR TAR RNA. However, TRBP binding to TAR RNA relieves its inhibitory action of translation and Dicer processes HIV-1 TAR RNA to generate TAR miRNA. However, whether the interaction between TRBP and Dicer is necessary for TAR RNA translation or TAR miRNA processing remains unclear. In this study, we constructed TRBP mutants that were unable to interact with Dicer by introducing mutations into amino acid residues necessary for the interaction. Furthermore, we established cell lines expressing such TRBP mutants. Then, we revealed that the TRBP–Dicer interaction is essential for both the TAR-containing RNA translation and the TAR miRNA processing in HIV-1. The Company of Biologists Ltd 2020-02-25 /pmc/articles/PMC7055394/ /pubmed/32051109 http://dx.doi.org/10.1242/bio.050435 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Komori, Chiaki
Takahashi, Tomoko
Nakano, Yuko
Ui-Tei, Kumiko
TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis
title TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis
title_full TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis
title_fullStr TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis
title_full_unstemmed TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis
title_short TRBP–Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis
title_sort trbp–dicer interaction may enhance hiv-1 tar rna translation via tar rna processing, repressing host-cell apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055394/
https://www.ncbi.nlm.nih.gov/pubmed/32051109
http://dx.doi.org/10.1242/bio.050435
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