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Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine zipper protein (HBZ) is expressed in all cases of ATL and is directly associated with virus pathogenicity. The two isoforms of the HBZ protein are synthesized from antisense...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237760/ https://www.ncbi.nlm.nih.gov/pubmed/30215750 http://dx.doi.org/10.1093/nar/gky802 |
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author | Cáceres, C Joaquín Angulo, Jenniffer Lowy, Fernando Contreras, Nataly Walters, Beth Olivares, Eduardo Allouche, Delphine Merviel, Anne Pino, Karla Sargueil, Bruno Thompson, Sunnie R López-Lastra, Marcelo |
author_facet | Cáceres, C Joaquín Angulo, Jenniffer Lowy, Fernando Contreras, Nataly Walters, Beth Olivares, Eduardo Allouche, Delphine Merviel, Anne Pino, Karla Sargueil, Bruno Thompson, Sunnie R López-Lastra, Marcelo |
author_sort | Cáceres, C Joaquín |
collection | PubMed |
description | Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine zipper protein (HBZ) is expressed in all cases of ATL and is directly associated with virus pathogenicity. The two isoforms of the HBZ protein are synthesized from antisense messenger RNAs (mRNAs) that are either spliced (sHBZ) or unspliced (usHBZ) versions of the HBZ transcript. The sHBZ and usHBZ mRNAs have entirely different 5′untranslated regions (5′UTR) and are differentially expressed in cells, with the sHBZ protein being more abundant. Here, we show that differential expression of the HBZ isoforms is regulated at the translational level. Translation initiation of the usHBZ mRNA relies on a cap-dependent mechanism, while the sHBZ mRNA uses internal initiation. Based on the structural data for the sHBZ 5′UTR generated by SHAPE in combination with 5′ and 3′ deletion mutants, the minimal region harboring IRES activity was mapped to the 5′end of the sHBZ mRNA. In addition, the sHBZ IRES recruited the 40S ribosomal subunit upstream of the initiation codon, and IRES activity was found to be dependent on the ribosomal protein eS25 and eIF5A. |
format | Online Article Text |
id | pubmed-6237760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62377602018-11-21 Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein Cáceres, C Joaquín Angulo, Jenniffer Lowy, Fernando Contreras, Nataly Walters, Beth Olivares, Eduardo Allouche, Delphine Merviel, Anne Pino, Karla Sargueil, Bruno Thompson, Sunnie R López-Lastra, Marcelo Nucleic Acids Res RNA and RNA-protein complexes Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine zipper protein (HBZ) is expressed in all cases of ATL and is directly associated with virus pathogenicity. The two isoforms of the HBZ protein are synthesized from antisense messenger RNAs (mRNAs) that are either spliced (sHBZ) or unspliced (usHBZ) versions of the HBZ transcript. The sHBZ and usHBZ mRNAs have entirely different 5′untranslated regions (5′UTR) and are differentially expressed in cells, with the sHBZ protein being more abundant. Here, we show that differential expression of the HBZ isoforms is regulated at the translational level. Translation initiation of the usHBZ mRNA relies on a cap-dependent mechanism, while the sHBZ mRNA uses internal initiation. Based on the structural data for the sHBZ 5′UTR generated by SHAPE in combination with 5′ and 3′ deletion mutants, the minimal region harboring IRES activity was mapped to the 5′end of the sHBZ mRNA. In addition, the sHBZ IRES recruited the 40S ribosomal subunit upstream of the initiation codon, and IRES activity was found to be dependent on the ribosomal protein eS25 and eIF5A. Oxford University Press 2018-11-16 2018-09-12 /pmc/articles/PMC6237760/ /pubmed/30215750 http://dx.doi.org/10.1093/nar/gky802 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA and RNA-protein complexes Cáceres, C Joaquín Angulo, Jenniffer Lowy, Fernando Contreras, Nataly Walters, Beth Olivares, Eduardo Allouche, Delphine Merviel, Anne Pino, Karla Sargueil, Bruno Thompson, Sunnie R López-Lastra, Marcelo Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein |
title | Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein |
title_full | Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein |
title_fullStr | Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein |
title_full_unstemmed | Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein |
title_short | Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein |
title_sort | non-canonical translation initiation of the spliced mrna encoding the human t-cell leukemia virus type 1 basic leucine zipper protein |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237760/ https://www.ncbi.nlm.nih.gov/pubmed/30215750 http://dx.doi.org/10.1093/nar/gky802 |
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