TAR RNA Binding Protein 2 (TARBP2) is a crucial protein involved in various cellular processes, particularly in the regulation of gene expression. It was first identified and cloned due to its high affinity binding to the trans-activation response (TAR) RNA element of the Human Immunodeficiency Virus (HIV-1) . This protein plays a significant role in the RNA-induced silencing complex (RISC), serving as a co-factor for Dicer in the processing of precursor microRNAs (pre-miRNAs) into mature microRNAs (miRNAs) .
TARBP2 contains two double-stranded RNA binding domains (RBDs), which are essential for its interaction with RNA molecules . These domains enable TARBP2 to bind to the bulge and loop regions of the HIV-1 TAR RNA regulatory element, thereby activating HIV-1 gene expression in synergy with the viral Tat protein . Additionally, TARBP2 is involved in the modulation of transient receptor potential canonical 4 (TRPC4) protein, influencing calcium ion (Ca²⁺) entry in endothelial, smooth muscle, and neuronal cells .
One of the primary functions of TARBP2 is its involvement in the biogenesis of miRNAs. In eukaryotic cells, primary microRNA transcripts (pri-miRNAs) are transcribed by RNA polymerase II and processed by Drosha in the nucleus to form pre-miRNA precursors . These precursors are then transported to the cytoplasm, where they are further processed by Dicer into mature miRNAs. TARBP2 binds directly to Dicer and is crucial for the activity of miRNA-mediated RNA silencing . The TARBP2-Ago2 complex within the RISC is essential for optimal miRNA-guided post-transcriptional gene silencing .
TARBP2 interacts with various intracellular proteins involved in protein synthesis, RNA modifications and processing, DNA transcription, and cell proliferation . These interactions suggest that TARBP2 may cooperate with other cellular factors in miRNA processing and RNA interference by the RISC complex . Additionally, TARBP2 can inhibit the interferon-induced double-stranded RNA-activated protein kinase R (PKR), further highlighting its multifaceted role in cellular processes .
Recombinant human TARBP2 is produced using recombinant DNA technology, allowing for the expression and purification of the protein in a controlled laboratory environment. This recombinant form is used in various research applications to study the protein’s structure, function, and interactions with other cellular components .