Global Regulatory Functions of the Human CCR4-NOT Complex in mRNA Deadenylation and Decay
- 1University of Minnesota
Abstract
Shortening of the poly(A) tail initiates mRNA decay, and the human CCR4-NOT is the principal cytoplasmic deadenylase. Although its subunits have been defined, their functions have not been comprehensively evaluated in cells. We depleted each CCR4-NOT subunit and measured transcriptome-wide effects. CCR4-NOT regulated transcripts from thousands of genes, many of which associated with the complex in cells. Distinct groups of transcripts responded according to the modular organization of the complex, while subsets exhibited unique responses to specific subunits. Poly(A) tail analysis revealed that the CNOT7 and CNOT8 deadenylases are the predominant regulators of poly(A) tail length in these cells. CCR4-NOT targets were enriched in regulatory pathways including cell proliferation, apoptosis, stress responses, and cancer-related processes. Bioinformatic analysis identified sequence determinants and candidate recruitment factors associated with CCR4-NOT regulation. The results define the breadth and specificity of CCR4-NOT-mediated mRNA decay and provide a resource for dissecting regulatory mechanisms and biological roles.
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BibTeX
@misc{mckenney2026global,
title = {{Global Regulatory Functions of the Human CCR4-NOT Complex in mRNA Deadenylation and Decay}},
author = {K. M. McKenney and M. Nevo and R. P. Connacher and K. Rebbani and Z. Luo and E. B. Dunshee and M. R. Fabian and E. Valkov and J. Brumbaugh and A. C. Goldstrohm},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755734},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755734v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Global Regulatory Functions of the Human CCR4-NOT Complex in mRNA Deadenylation and Decay
AU - K. M. McKenney
AU - M. Nevo
AU - R. P. Connacher
AU - K. Rebbani
AU - Z. Luo
AU - E. B. Dunshee
AU - M. R. Fabian
AU - E. Valkov
AU - J. Brumbaugh
AU - A. C. Goldstrohm
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755734
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755734v1
AB - Shortening of the poly(A) tail initiates mRNA decay, and the human CCR4-NOT is the principal cytoplasmic deadenylase. Although its subunits have been defined, their functions have not been comprehensively evaluated in cells. We depleted each CCR4-NOT subunit and measured transcriptome-wide effects. CCR4-NOT regulated transcripts from thousands of genes, many of which associated with the complex in cells. Distinct groups of transcripts responded according to the modular organization of the complex, while subsets exhibited unique responses to specific subunits. Poly(A) tail analysis revealed that the CNOT7 and CNOT8 deadenylases are the predominant regulators of poly(A) tail length in these cells. CCR4-NOT targets were enriched in regulatory pathways including cell proliferation, apoptosis, stress responses, and cancer-related processes. Bioinformatic analysis identified sequence determinants and candidate recruitment factors associated with CCR4-NOT regulation. The results define the breadth and specificity of CCR4-NOT-mediated mRNA decay and provide a resource for dissecting regulatory mechanisms and biological roles.
ER -