The HIV Tat protein affects processing of ribosomal RNA precursor

Donatella Ponti,Piero A Battaglia,Gian Carlo Bellenchi,Maria Troiano,Franca Gigliani

doi:10.1186/1471-2121-9-32

Abstract

BackgroundInside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.ResultsTo clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in Drosophila melanogaster strain transgenic for HIV-tat gene. Here we show that Tat localizes in the nucleoli of Drosophila oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation.ConclusionOur data contribute to understanding the function of Tat in the nucleolus, where ribosomal RNA synthesis and cell cycle control take place. The impairment of nucleolar pre-rRNA maturation through the interaction of Tat with fibrillarin-U3snoRNA complex suggests a process by which the virus modulates host response, thus contributing to apoptosis and protein shut-off in HIV-uninfected cells.

Highlights

Inside the cell, the HIV transcriptional activator (Tat) protein is mainly found in the nucleus and nucleolus
Tat expressed by heat shock treatment, colocalizes with fibrillarin in the nucleolus of Drosophila cells Nucleolar localization of the HIV Tat protein has been extensively shown using several cellular systems [13,14,15,16,17]
To shed light on the effects of the nucleolar localization of Tat, we determined whether it localizes in the nucleolus of tat transgenic Drosophila melanogaster cells, where its expressions is driven under the control of the heat shock promoter [10]

Summary

Introduction

The HIV Tat protein is mainly found in the nucleus and nucleolus. Tat affects several cellular functions by inducing angiogenesis [3,4], cell proliferation and apoptosis [5]. It has been shown that in both infected and uninfected cells, Tat localizes in the nucleolus [13] and that the nucleolar accumulation of Tat occurs via the highly conserved stretch of basic amino acids that acts as a nucleolar localization signal (NoLS) [14,15,16,17]. The nucleolus is a highly structured and dynamic organelle involved in the transcription and maturation of rRNA and ribosome biogenesis as well as in apoptosis and in cell cycle control [18]. Nucleolar localization of TAR impairs virus progression [20,21]

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Conclusion