1. Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein
- Author
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Eduardo Olivares, Karla Pino, Fernando Lowy, C. Joaquín Cáceres, Beth Walters, Marcelo López-Lastra, Jenniffer Angulo, Anne Merviel, Bruno Sargueil, Sunnie R. Thompson, Delphine Allouche, Nataly Contreras, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Laboratorio de Virología Molecular [Santiago, Chile] (Instituto Milenio de Inmunología e Inmunoterapia), Pontificia Universidad Católica de Chile (UC)-Centro de Investigaciones Medicas [Santiago, Chile] (Escuela de Medicina), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Centro de Investigaciones Medicas [Santiago, Chile] (Escuela de Medicina)-Pontificia Universidad Católica de Chile (UC)
- Subjects
0301 basic medicine ,Gene Expression Regulation, Viral ,Leucine zipper ,[SDV]Life Sciences [q-bio] ,RNA Splicing ,Retroviridae Proteins ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Biology ,03 medical and health sciences ,Eukaryotic translation ,Ribosomal protein ,Chlorocebus aethiops ,Genetics ,RNA and RNA-protein complexes ,Animals ,Humans ,Protein Isoforms ,Eukaryotic Small Ribosomal Subunit ,RNA, Messenger ,Peptide Chain Initiation, Translational ,ComputingMilieux_MISCELLANEOUS ,Messenger RNA ,Human T-lymphotropic virus 1 ,RNA ,Cell biology ,Internal ribosome entry site ,030104 developmental biology ,Basic-Leucine Zipper Transcription Factors ,HEK293 Cells ,COS Cells ,RNA, Viral ,5' Untranslated Regions ,Corrigendum ,EIF5A ,HeLa Cells - Abstract
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.
- Published
- 2018
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