The exosome complex establishes a barricade to erythroid maturation

McIver, Skye C; Kang, Yoon A.; DeVilbiss, Andrew W.; O’Driscoll, Chelsea A.; Ouellette, Jonathan N.; Pope, Nathaniel J.; Campreciós, Genís; Chang, Chan Jung; Yang, David T.; Bouhassira, Eric E.; Ghaffari, Saghi; Bresnick, Emery H.

doi:10.1182/blood-2014-04-571083

Cited by 60 publications

(79 citation statements)

References 71 publications

(76 reference statements)

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“…Recent work has also illuminated a role for the exosome during erythropoiesis, the process through which hematopoietic stem cells differentiate into erythrocytes (McIver et al 2014(McIver et al , 2016. In this process, the balance between hematopoietic stem cell differentiation and proliferation is critical: Proliferation can lead to tumor formation, while differentiation can exhaust the supply of stem cells.…”

Section: Proliferation and Differentiationmentioning

confidence: 99%

“…GATA-1 and Foxo-3 are master transcription factors that control differentiation during erythropoiesis, and both down-regulate expression of Exosc8, an Exo9 subunit (Table 1). Interestingly, shRNA knockdown of exosome core subunits in hematopoietic stem cells resulted in an accumulation of GATA-1-and Foxo-3-regulated transcripts, suggesting that the exosome may counter differentiation by degrading these transcripts in the absence of erythropoietin (McIver et al 2014), similar to a role proposed for the exosome in maintaining a proliferative state in human skin stem cells via selective targeting of the GRLH mRNA (Mistry et al 2012). Furthermore, hematopoietic stem cells depleted of exosome components were nonresponsive to SCF due to decreased levels of its cognate receptor tyrosine kinase, Kit, although they remained responsive to erythropoietin (McIver et al 2016).…”

Section: Proliferation and Differentiationmentioning

confidence: 99%

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Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

2017

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The eukaryotic RNA exosome is an essential and conserved protein complex that can degrade or process RNA substrates in the 3 ′ -to-5 ′ direction. Since its discovery nearly two decades ago, studies have focused on determining how the exosome, along with associated cofactors, achieves the demanding task of targeting particular RNAs for degradation and/or processing in both the nucleus and cytoplasm. In this review, we highlight recent advances that have illuminated roles for the RNA exosome and its cofactors in specific biological pathways, alongside studies that attempted to dissect these activities through structural and biochemical characterization of nuclear and cytoplasmic RNA exosome complexes.

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Section: Proliferation and Differentiationmentioning

confidence: 99%

Section: Proliferation and Differentiationmentioning

confidence: 99%

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

2017

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“…Genes important for erythroid cell differentiation, such as Myb, Tal1, Cdk6, and the recently described Exosc2 gene, which is part of the exosome complex (51), did not show any change in their expression levels (q value, Ͼ0.4). Most of the aforementioned genes were found to be bound by GATA1 in their regulatory sequences but in many cases were bound at different developmental stages (40,47,51,52). Specifically for Myb, Cdk6, and Exosc2, the GATA1 peaks were found to present at levels below the cutoff level in the E12.5 fetal liver (40).…”

Section: Resultsmentioning

confidence: 99%

TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis

Papadopoulos

Gutiérrez

Demmers

et al. 2015

Molecular and Cellular Biology

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The ordered assembly of a functional preinitiation complex (PIC), composed of general transcription factors (GTFs), is a prerequisite for the transcription of protein-coding genes by RNA polymerase II. TFIID, comprised of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs), is the GTF that is thought to recognize the promoter sequences allowing site-specific PIC assembly. Transcriptional cofactors, such as SAGA, are also necessary for tightly regulated transcription initiation. The contribution of the two TAF10-containing complexes (TFIID, SAGA) to erythropoiesis remains elusive. By ablating TAF10 specifically in erythroid cells in vivo, we observed a differentiation block accompanied by deregulated GATA1 target genes, including Gata1 itself, suggesting functional cross talk between GATA1 and TAF10. Additionally, we analyzed by mass spectrometry the composition of TFIID and SAGA complexes in mouse and human cells and found that their global integrity is maintained, with minor changes, during erythroid cell differentiation and development. In agreement with our functional data, we show that TAF10 interacts directly with GATA1 and that TAF10 is enriched on the GATA1 locus in human fetal erythroid cells. Thus, our findings demonstrate a cross talk between canonical TFIID and SAGA complexes and cell-specific transcription activators during development and differentiation. Initiation of RNA polymerase II (RNA pol II) transcription in eukaryotes is a process involving the stepwise recruitment and assembly of the preinitiation complex (PIC) at the core promoter of a transcriptional unit. Transcription factor TFIID, comprised of the TATA binding protein (TBP) and a series of TBP-associated factors (TAFs), is the general transcription factor (GTF) that, by recognizing the promoter sequences and surrounding chromatin marks, allows the site-specific assembly of the PIC (see reference 1 and references therein). Binding of the TFIID complex is aided by TFIIA and is followed by the remainder of the general transcription machinery, including TFIIB, RNA pol II/TFIIF, TFIIE, and TFIIH complexes. Additional cofactors, including the Mediator complex, histone modifiers, and chromatin remodelers, facilitate the communication between gene-specific transcription factors and the general transcription machinery.The TFIID complex binds not only to TATA box-containing promoters but also to TATA-less promoters, and this led to the idea that TAFs could provide TFIID with additional functional features (2, 3). Indeed, 9 out of 13 TAFs contain a histone fold domain (HFD) (4) favoring the formation of TAF heterodimers. For instance, the TAF6-TAF9 heterodimer has been found to bind promoter elements downstream of the TATA box (5-7) and is a direct target of transcriptional activators (8, 9). Moreover, it has been shown that TAF knockouts (KOs) and in vitro TAF-knockdown experiments result in both the down-and upregulated expression of subsets of genes (10, 11). All these results together suggest that TFIID is a highly flexible r...

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“…The potential roles of GATAs family zinc finger transcription factors in regulating genes encoding components of the autophagy machinery attract many scientists' attention [183][184][185][186]. The current study focused on GATA1 and GATA4, and the research on other members is just at the start [182].…”

Section: Other Important Transcription Factors Of Autophagy Regulatiomentioning

confidence: 96%

“…The current study focused on GATA1 and GATA4, and the research on other members is just at the start [182]. It is generally accepted that GATA1 and GATA4 of the GATAs family show different transcriptional regulation role of autophagy [183]. GATA1 can directly bind at the promoters of ATG4, ATG8, LC3, ATG12, and Bnip3 to upregulate autophagy flux [184].…”

Section: Other Important Transcription Factors Of Autophagy Regulatiomentioning

confidence: 99%

The update on transcriptional regulation of autophagy in normal and pathologic cells: A novel therapeutic target

Zhang

Guo

Zhao

et al. 2015

Biomedicine & Pharmacotherapy

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The exosome complex establishes a barricade to erythroid maturation

Abstract: Key Points Exosome complex components are endogenous suppressors of erythroid cell maturation. GATA-1 and Foxo3 transcriptionally repress exosome complex components, thus abrogating the erythroid maturation blockade.

Cited by 60 publications

References 71 publications

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis

The update on transcriptional regulation of autophagy in normal and pathologic cells: A novel therapeutic target

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