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HTLV\u20101 transcribes sense and two antisense messenger RNAs (mRNAs). The spliced and unspliced antisense mRNA encode the HTLV\u20101 basic zipper factor (HBZ). The sense mRNA can initiate translation using a cap\u2010 or internal ribosomal entry site (IRES)\u2010mediated mechanism (HTLV\u20101 IRES). The spliced antisense mRNA initiates translation via the sHBZ IRES. Using bicistronic vectors harboring the 5\u2032\u2010untranslated region of the HTLV\u20101 sense or spliced antisense mRNAs in their intercistronic space, we evaluated the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), ELAV\u2010like protein 1 (ELAVL1; also known as HuR), and polypyrimidine tract\u2010binding protein 1 (PTB) as regulators of the HTLV\u20101 IRES and sHBZ IRES function. Results show that PTB is not an IRES\u2010transacting factor (ITAF) for either IRES, whereas hnRNPA1 promotes both. However, protein arginine N\u2010methyltransferase 5 (PRMT5)\u2010induced symmetrical dimethylation of arginine residues in hnRNPA1, required to stimulate the HTLV\u20101 IRES, plays no role in sHBZ IRES activity. HuR overexpression reduces both HTLV\u20101 IRES and sHBZ IRES activity. The effect of hnRNPA1 and HuR over the IRESs is lost when both proteins are overexpressed together. When heterogeneous nuclear ribonucleoprotein K (hnRNPK), an ITAF for the HTLV\u20101 IRES but not for the sHBZ IRES, is overexpressed with HuR, HTLV\u20101 IRES is stimulated, whereas sHBZ IRES activity is reduced. Consequently, ITAFs or combinations of ITAFs differentially modulated the HTLV\u20101 IRES and sHBZ IRES activity, indicating that these IRESs are under translational control mediated by different subsets of ITAFs.<\/jats:p>","DOI":"10.1111\/febs.70361","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T15:55:41Z","timestamp":1764950141000},"page":"2098-2118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HnRNPA1<\/scp>\n                    and\n                    <scp>HuR<\/scp>\n                    , but not\n                    <scp>PTB<\/scp>\n                    , modulate cap\u2010independent translation initiation from sense and antisense human T\u2010cell lymphotropic virus type 1\n                    <scp>\n                      mRNA\n                      <b>s<\/b>\n                    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