The HIV Tat protein affects processing of ribosomal RNA precursor.
BACKGROUND
Inside 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.


RESULTS
To 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.


CONCLUSIONS
Our 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.
Ponti
Donatella
D
Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma, Italia. donatella.ponti@uniroma1.it
Troiano
Maria
M
Bellenchi
Gian Carlo
GC
Battaglia
Piero A
PA
Gigliani
Franca
F
D000818:Animals; D030801:Animals, Genetically Modified; D002466:Cell Nucleolus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D020537:RNA, Small Nucleolar / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D012322:RNA Precursors; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; C117378:RNA, U3 small nucleolar; C047458:fibrillarin; D054322:tat Gene Products, Human Immunodeficiency Virus