Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm.
Mol Cell
; 42(4): 489-99, 2011 May 20.
Article
em En
| MEDLINE
| ID: mdl-21596313
ABSTRACT
Poly(ADP-ribose) is a major regulatory macromolecule in the nucleus, where it regulates transcription, chromosome structure, and DNA damage repair. Functions in the interphase cytoplasm are less understood. Here, we identify a requirement for poly(ADP-ribose) in the assembly of cytoplasmic stress granules, which accumulate RNA-binding proteins that regulate the translation and stability of mRNAs upon stress. We show that poly(ADP-ribose), six specific poly(ADP-ribose) polymerases, and two poly(ADP-ribose) glycohydrolase isoforms are stress granule components. A subset of stress granule proteins, including microRNA-binding Argonaute family members Ago1-4, are modified by poly(ADP-ribose), and such modification increases upon stress, a condition when both microRNA-mediated translational repression and microRNA-directed mRNA cleavage are relieved. Similar relief of repression is also observed upon overexpression of specific poly(ADP-ribose) polymerases or, conversely, upon knockdown of glycohydrolase. We conclude that poly(ADP-ribose) is a key regulator of posttranscriptional gene expression in the cytoplasm.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poli Adenosina Difosfato Ribose
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Estresse Fisiológico
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Regulação da Expressão Gênica
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Citoplasma
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Grânulos Citoplasmáticos
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MicroRNAs
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article