Global Regulatory Functions of the Human CCR4-NOT Complex in mRNA Deadenylation and Decay
McKenney, K. M.; Nevo, M.; Connacher, R. P.; Rebbani, K.; Luo, Z.; Dunshee, E. B.; Fabian, M. R.; Valkov, E.; Brumbaugh, J.; Goldstrohm, A. C.
Show 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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Angel Wing: a class of alternative splicing regulators in animals 95%
- Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance 94%
- Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome 94%
Similar papers in this journal
- Identification of human genetic variants controlling circular RNA expression 94%
- eRNAs Modulate mRNA Stability and Translation Efficiency to Bridge Transcriptional and Post-transcriptional Gene Regulation 94%
- Degradation factor 1, Def1, regulates mRNA translation and decay through Ccr4-Not-dependent ubiquitylation of the ribosome. 93%
Similar papers in this journal
Similar papers in this journal
- Zinc finger RNA binding protein Zn72D regulates ADAR-mediated RNA editing in neurons 95%
- 3’UTR Remodelling of Axonal Transcripts in Sympathetic Neurons 95%
- CLIP-Seq and massively parallel functional analysis of the CELF6 RNA binding protein reveals a role in destabilizing synaptic gene mRNAs through interaction with 3’UTR elements in vivo 95%
Similar papers in this journal
- Asynchronous microexon splicing of LSD1 and PHF21A during neurodevelopment 92%
- DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation 92%
- Biochemical characterizations of Pontocerebellar Hypoplasia linked mutations of Target of Egr1 (TOE1) reveal impacts on thermal stability, ribonuclease activity, and oligomerization 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.