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Cleavage and polyadenylation specificity factor subunit 4 (CPSF4) is an essential component of the mRNA 3′-end processing machinery, functioning within the CPSF complex to recognize the AAUAAA polyadenylation signal and facilitate the cleavage and polyadenylation of nascent pre-mRNAs[1][2][5]. CPSF4 contains multiple zinc finger domains and can exist in diverse splice isoforms[2][5]. Beyond its canonical role, CPSF4 also interacts with transcriptional regulators (e.g., CBP) and cancer-related promoters to modulate oncogenic transcriptional programs and cellular proliferation[2][4]. In viral infection, notably influenza, CPSF4 is hijacked by the NS1 protein to disrupt host mRNA processing[3][5]. In cancer, CPSF4 is frequently upregulated, promoting tumor cell proliferation, survival, and metastasis, and is associated with poor prognosis[1][2][4]. Knockdown of CPSF4 impairs cancer cell growth and induces apoptosis by inhibiting PI3K/AKT and MAPK signaling pathways[1][2]. CPSF4 is thus considered a promising therapeutic target and biomarker for cancers such as lung adenocarcinoma and prostate cancer[1][4].
siRNA/antisense approaches: knockdown leads to suppression of cell proliferation, induction of apoptosis, and cell cycle arrest in cancer models. Viral inhibitor: influenza NS1 protein binds and sequesters CPSF4, inhibiting host mRNA processing.
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