{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CSTF2 (the 64‐kDa subunit of cleavage stimulation factor, CstF‑64) is a core component of the pre‐mRNA 3′ processing machinery that mediates both canonical cleavage/polyadenylation and alternative polyadenylation (APA). Its RNA recognition motif confers the ability to bind GU-rich elements downstream of polyadenylation sites, a capacity that is modulated by intrinsic domain dynamics allowing flexible yet specific interactions with a variety of target sequences."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " CSTF2 not only ensures the efficient assembly of 3′ end processing complexes through interactions with proteins such as symplekin and CstF-77, but it also plays a pivotal role in determining poly(A) site choice. Variations in CSTF2 expression levels or functionality have been linked to shifts in APA profiles—for instance, elevated CSTF2 activity is associated with preferential use of proximal poly(A) sites, resulting in 3′ untranslated region shortening that can impact mRNA stability and translational efficiency, a phenomenon observed in various cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, CSTF2 is subject to regulation by and interplay with other RNA-binding proteins. For example, in B lymphocytes, competition between CSTF2 and hnRNP F for binding downstream of the polyadenylation signal is a key determinant in switching between secretory and membrane-bound immunoglobulin heavy-chain mRNA isoforms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, viral strategies can target CSTF2 to impair host gene expression; cleavage of CSTF2 by viral proteases disrupts normal polyadenylation, leading to accumulation of unprocessed pre-mRNAs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The precise regulation of CSTF2 levels is critical during cellular transitions. For instance, its abundance increases during cell cycle progression (the G0 to S phase transition) to support the surge in polyadenylated RNA required for proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and its proper intracellular localization and stability depend on its interactions with other core factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, CSTF2 is an essential 3′ end processing factor whose dynamic RNA-binding properties and interactions with additional processing components critically influence mRNA maturation and the selection of alternative polyadenylation sites, thereby modulating gene expression in both physiological and pathological contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "José Manuel Pérez Cañadillas, Gabriele Varani "}, {"type": "b", "children": [{"type": "t", "text": "Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg259"}], "href": "https://doi.org/10.1093/emboj/cdg259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12773396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12773396"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pritilekha Deka, P K Rajan, Jose Manuel Perez-Canadillas, et al. 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