| CNOT7 is a catalytic subunit of the CCR4–NOT complex, one of the main cellular deadenylases that controls mRNA stability and translation by shortening poly(A) tails at the 3′ end of transcripts. The protein adopts an RNase D–like exonuclease fold that coordinates divalent metal ions in its active site and binds to poly(A) tails so that adenosine residues are positioned for stepwise 3′–5′ phosphodiester bond hydrolysis, generating shortened intermediates that are then handed off to exonucleases that complete decay. CNOT7 is anchored into the CCR4–NOT scaffold through contacts with the central MIF4G domain of CNOT1 and bridges to CCR4 family deadenylases, creating a modular complex where different catalytic subunits and associated RNA‑binding proteins can converge on the same mRNA. Recruitment of CCR4–NOT–CNOT7 assemblies to specific transcripts occurs through interactions with adapter proteins and RNA‑binding factors, including those that recognize AU‑rich elements or microRNA‑loaded Argonaute complexes, so CNOT7 activity is directed to selected mRNAs in response to developmental programs, signaling cues, or stress. Deadenylation driven by CNOT7 reduces poly(A)‑binding protein occupancy, weakens the closed‑loop translation initiation structure, and promotes decapping and 5′–3′ decay, which together shift transcripts from actively translated pools into silenced or degraded states and reshape gene‑expression profiles on a genome‑wide scale. CNOT7 and its paralog CNOT8 catalytic subunits are required to maintain global deadenylation capacity and cell viability, and the combined loss leads to widespread poly(A) tail lengthening, accumulation of otherwise short‑lived mRNAs, and strong defects in proliferation. Alternative splicing generates CNOT7 isoforms that differ in their C‑terminal regions and in their ability to engage specific partners, providing an additional layer of control over which transcripts are targeted and how deadenylation is coupled to translational repression or mRNA localization in specialized cell types such as neurons. |
