Abstract
ABSTRACTThe transactivating response (TAR) RNA-binding protein (TRBP) has been identified as a double-stranded RNA (dsRNA)-binding protein, which associates with a stem-loop region known as the TAR element in human immunodeficiency virus-1 (HIV-1). However, TRBP is also known to be an enhancer of RNA silencing, interacting with Dicer, an enzyme that belongs to the RNase III family. Dicer cleaves long dsRNA into small dsRNA fragments called small interfering RNA or microRNA (miRNA) to mediate RNA silencing. During HIV-1 infection, TAR RNA-mediated translation is suppressed by the secondary structure of 5′UTR TAR RNA. However, TRBP binding to TAR RNA relieves its inhibitory action of translation and Dicer processes HIV-1 TAR RNA to generate TAR miRNA. However, whether the interaction between TRBP and Dicer is necessary for TAR RNA translation or TAR miRNA processing remains unclear. In this study, we constructed TRBP mutants that were unable to interact with Dicer by introducing mutations into amino acid residues necessary for the interaction. Furthermore, we established cell lines expressing such TRBP mutants. Then, we revealed that the TRBP–Dicer interaction is essential for both the TAR-containing RNA translation and the TAR miRNA processing in HIV-1.
Highlights
Human immunodeficiency virus-1 (HIV-1) is the causative virus of acquired immunodeficiency syndrome (AIDS) (Barre-Sinoussi et al, 1983; Gallo et al, 1984)
We revealed that the TRBP–Dicer interaction is essential for both the transactivating response (TAR)-containing RNA translation and the TAR miRNA processing in human immunodeficiency virus-1 (HIV-1)
We investigated whether Dicer collaboratively functions with TRBP in the inhibition of translational suppression of HIV-1 TAR RNA and whether Dicer is associated with TRBP in the TAR miRNA cleavage process
Summary
Human immunodeficiency virus-1 (HIV-1) is the causative virus of acquired immunodeficiency syndrome (AIDS) (Barre-Sinoussi et al, 1983; Gallo et al, 1984). They are capable of evading the immune response (Pawlak and Dikeakos, 2015), and protecting infected cells from apoptosis (Selliah et al 2003). Transactivating response (TAR) RNA-binding protein (TRBP) was first identified as a factor that binds to the stem-loop TAR RNA region of long terminal repeats (LTRs) on both the 5 - and 3 -ends of HIV-1 (Gatignol et al, 1991) (Fig. 1A). The full-length viral RNA (Berkhout et al, 1989) and the short ~60 nt non-processive TAR RNA with stem-loop structure, a substrate for the production of TAR miRNA (Harwig et al, 2016), are transcribed from the 5′ LTR. How Dicer recognises TAR RNA for processing remains unknown
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