Proteomics

Dataset Information

54

The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading


ABSTRACT: Background: The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNAsilencing pathways, exerting a pivotal role in microRNA maturation and activity, that in the cell nucleus is able to modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. The Estrogen Receptor beta (ERβ), a member of the nuclear receptor superfamily of trancriptional regulators, is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Results: Applying interaction proteomics coupled to mass spectrometry (MS) to characterize nuclear factors cooperating with ERβ in gene regulation, we identified AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo both in the nucleus and cytoplasm. ChIP-Seq demonstrated AGO2 association to a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ+ vs ERβ- cells, and before and after AGO2 knock-down in ERβ+ cells, revealed a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggested involvement of the nuclear receptor in RISC loading, indicating that it may able to control directly also mRNA translation efficiency and stability. Conclusions: These results demonstrate that AGO2 is a pleiotropic functional partner of ERβ in BC cells, indicating that both factors are endowed with multiple roles in the control of BC cell functions.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo sapiens  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Tuula Nyman  

LAB HEAD: Tuula Nyman

PROVIDER: PXD006280 | Pride | 2017-09-20

REPOSITORIES: Pride

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BACKGROUND:The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better progn  ...[more]

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