{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed the multifaceted roles of double‐stranded RNA‐binding proteins—including PACT (PRKRA), TRBP, and RAX—and their regulation of the dsRNA-activated protein kinase PKR in diverse cellular stress responses, antiviral defense, and developmental processes. Genetic loss-of-function models have demonstrated that disruption of these proteins can lead to defects in ear, craniofacial, and pituitary development as well as abnormalities in neural migration and apoptosis. In addition, these studies indicate that cellular stress, whether induced by chemical agents or viral infection, modulates the interactions between these proteins, thereby influencing PKR activation and downstream translational control and cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, it is now evident that these dsRNA-binding proteins play critical roles in the biogenesis and function of microRNAs (miRNAs), thereby linking posttranscriptional regulation to cell differentiation and stress responses. Investigations into the roles of cofactors such as TARBP2 and PACT in miRNA processing have shown that alterations in their function can shift miRNA expression profiles, with downstream effects on cellular proliferation, differentiation, and signaling pathways—including those governing epithelial renewal and metabolic responses. These findings highlight the complexity of miRNA regulation during both tissue development and the response to external stimuli."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the oncologic context, miR-519e-5p has emerged as a critical regulator in breast cancer by targeting CTP synthase 1 (CTPS1). Studies have demonstrated that miR-519e-5p is downregulated in breast cancer tissues and cell lines, resulting in derepression of its target CTPS1. Elevated CTPS1 expression, in turn, promotes increased cellular proliferation, migration, invasion, and epithelial–mesenchymal transition—a constellation of changes that drive tumor progression. Conversely, enforced expression of miR-519e-5p or knockdown of CTPS1 attenuates these malignant characteristics, and elevated serum levels of CTPS1 in patients correlate with clinical indicators such as age, HER-2 index, and tumor staging. These findings underscore the miR-519e/CTPS1 axis as a promising target for therapeutic intervention in breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard L Bennett, William L Blalock, W Stratford May "}, {"type": "b", "children": [{"type": "t", "text": "Serine 18 phosphorylation of RAX, the PKR activator, is required for PKR activation and consequent translation inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M403321200"}], "href": "https://doi.org/10.1074/jbc.M403321200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15299031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15299031"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Theresa M Rowe, Mark Rizzi, Keiko Hirose, et al. 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