PABP Cooperates with the CCR4-NOT Complex to Promote mRNA Deadenylation and Block Precocious Decay.
Mol Cell
; 70(6): 1081-1088.e5, 2018 06 21.
Article
em En
| MEDLINE
| ID: mdl-29932901
ABSTRACT
Multiple deadenylases are known in vertebrates, the PAN2-PAN3 (PAN2/3) and CCR4-NOT (CNOT) complexes, and PARN, yet their differential functions remain ambiguous. Moreover, the role of poly(A) binding protein (PABP) is obscure, limiting our understanding of the deadenylation mechanism. Here, we show that CNOT serves as a predominant nonspecific deadenylase for cytoplasmic poly(A)+ RNAs, and PABP promotes deadenylation while preventing premature uridylation and decay. PAN2/3 selectively trims long tails (>â¼150 nt) with minimal effect on transcriptome, whereas PARN does not affect mRNA deadenylation. CAF1 and CCR4, catalytic subunits of CNOT, display distinct activities CAF1 trims naked poly(A) segments and is blocked by PABPC, whereas CCR4 is activated by PABPC to shorten PABPC-protected sequences. Concerted actions of CAF1 and CCR4 delineate the â¼27 nt periodic PABPC footprints along shortening tail. Our study unveils distinct functions of deadenylases and PABPC, re-drawing the view on mRNA deadenylation and regulation.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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RNA Mensageiro
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Estabilidade de RNA
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Proteínas de Ligação a Poli(A)
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Receptores CCR4
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Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article