Altmetric

Human immunodeficiency virus Tat associates with a specific set of cellular RNAs

Title: Human immunodeficiency virus Tat associates with a specific set of cellular RNAs
Authors: Bouwman, RD
Palser, A
Parry, CM
Coulter, E
Rasaiyaah, J
Kellam, P
Jenner, RG
Item Type: Journal Article
Abstract: Background Human Immunodeficiency Virus 1 (HIV-1) exhibits a wide range of interactions with the host cell but whether viral proteins interact with cellular RNA is not clear. A candidate interacting factor is the trans-activator of transcription (Tat) protein. Tat is required for expression of virus genes but activates transcription through an unusual mechanism; binding to an RNA stem-loop, the transactivation response element (TAR), with the host elongation factor P-TEFb. HIV-1 Tat has also been shown to alter the expression of host genes during infection, contributing to viral pathogenesis but, whether Tat also interacts with cellular RNAs is unknown. Results Using RNA immunoprecipitation coupled with microarray analysis, we have discovered that HIV-1 Tat is associated with a specific set of human mRNAs in T cells. mRNAs bound by Tat share a stem-loop structural element and encode proteins with common biological roles. In contrast, we do not find evidence that Tat associates with microRNAs or the RNA-induced silencing complex (RISC). The interaction of Tat with cellular RNA requires an intact RNA binding domain and Tat RNA binding is linked to an increase in RNA abundance in cell lines and during infection of primary CD4+ T cells by HIV. Conclusions We conclude that Tat interacts with a specific set of human mRNAs in T cells, many of which show changes in abundance in response to Tat and HIV infection. This work uncovers a previously unrecognised interaction between HIV and its host that may contribute to viral alteration of the host cellular environment.
Issue Date: 3-Jul-2014
Date of Acceptance: 18-Jun-2014
URI: http://hdl.handle.net/10044/1/69469
DOI: https://dx.doi.org/10.1186/1742-4690-11-53
ISSN: 1742-4690
Publisher: BioMed Central
Journal / Book Title: Retrovirology
Volume: 11
Issue: 1
Copyright Statement: © 2014 Bouwman et al.; licensee BioMed Central Ltd. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
Human immunodeficiency virus
Tat
RNA
Transcription factor
RNA immunoprecipitation
Microarray
T cell
MicroRNA
CHROMATIN-REMODELING COMPLEX
CD4(+) T-LYMPHOCYTES
LONG TERMINAL REPEAT
HIV-1 TAT
GENE-EXPRESSION
IN-VITRO
TRANSCRIPTIONAL ACTIVATION
TRANSACTIVATOR PROTEIN
UP-REGULATION
P BODIES
Base Sequence
CD4-Positive T-Lymphocytes
Cell Line
Gene Expression Regulation, Viral
HEK293 Cells
HIV Infections
HIV-1
Humans
MicroRNAs
Molecular Sequence Data
Protein Binding
RNA, Messenger
RNA-Binding Proteins
Transcription, Genetic
Transcriptional Activation
tat Gene Products, Human Immunodeficiency Virus
1103 Clinical Sciences
Publication Status: Published
Article Number: 53
Online Publication Date: 2014-07-03
Appears in Collections:Department of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons