CPSF4

CPSF4 Full Name

cleavage and polyadenylation specific factor 4, 30kDa

CPSF4 Introduction

CPSF4 encodes the 30 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF) complex, an essential multiprotein assembly that governs the 3′-end processing of nearly all eukaryotic messenger RNA precursors. The CPSF complex recognizes the canonical AAUAAA polyadenylation signal sequence within pre-mRNA and coordinates two tightly coupled enzymatic reactions: endonucleolytic cleavage at a defined site downstream of the signal, and subsequent addition of a poly(A) tail by poly(A) polymerase — a modification critical for mRNA stability, nuclear export, and translational efficiency. CPSF4 itself contains zinc finger motifs that directly contact the AAUAAA signal, and it serves as a nucleation point for assembling the broader 3′-end processing machinery. This protein is predominantly nuclear, consistent with its role in pre-mRNA maturation, and its function is essential for cell viability as global inhibition of CPSF4 activity results in accumulation of unprocessed transcripts and cell death.

Figure 1. The CPA machinery, and specifically the CPSF73 endonuclease subunit of the CPSF complex, cleaves the 3' ends of pre-mRNA transcripts, creating a site for untemplated polyadenylation that is typical of mature mRNAs. (Source: Wei L, et al. 2022)

Beyond its fundamental role in mRNA biogenesis, CPSF4 has been increasingly recognized as a contributor to cancer pathogenesis. In lung cancer, CPSF4 binds to the promoter region of the vascular endothelial growth factor (VEGF) gene and enhances its transcription, activating a VEGF/NRP2/TAZ signaling cascade that promotes a tumor-initiating cell phenotype and confers resistance to paclitaxel chemotherapy both in vitro and in vivo. In triple-negative breast cancer, CPSF4 drives metastatic progression by upregulating MDM4, a potent inhibitor of the tumor suppressor p53, thereby disabling p53-mediated growth restraint and facilitating invasive behavior. The oncogenic potential of CPSF4 is further underscored by its earlier identified role in upregulating telomerase reverse transcriptase expression in lung cancer cells, linking aberrant mRNA 3′-end processing to telomere maintenance and cellular immortalization. CPSF4 also occupies a unique position at the host-pathogen interface: the influenza A virus nonstructural protein NS1 directly binds CPSF4 to block host pre-mRNA 3′-end processing, selectively shutting off cellular gene expression while sparing viral transcripts — a mechanism that highlights the vulnerability of the polyadenylation machinery to viral subversion and identifies CPSF4 as a potential antiviral target.

Alternate Names for CPSF4

CPSF4; cleavage and polyadenylation specific factor 4, 30kDa; NAR; NEB1; CPSF30; cleavage and polyadenylation specificity factor subunit 4; neb-1; no arches homolog; CPSF 30 kDa subunit; no arches-like zinc finger protein

• 1. Wei L, et al. Regulation of the Alternative Neural Transcriptome by ELAV/Hu RNA Binding Proteins. Front Genet. 2022 Feb 23;13:848626.
  2. Lee K, et al. CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4. Signal Transduct Target Ther. 2021 May 19;6(1):184.