Molecular Composition of IMP1 Ribonucleoprotein Granules

Jønson, Lars; Vikesaa, Jonas; Krogh, Anders; Nielsen, Lars K.; Hansen, Thomas V.O.; Borup, Rehannah; Johnsen, Anders H.; Christiansen, Jan; Nielsen, Finn Cilius

doi:10.1074/mcp.m600346-mcp200

Cited by 220 publications

(236 citation statements)

References 58 publications

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“…Initially, to identify mRNAs that potentially interact with IGF2BP1, IGF2BP1 immunoprecipitation was performed followed by RNASeq analysis of coprecipitating RNA. As predicted by the prevalence of the IGF2BP1-binding motif as well as earlier studies of mRNA binding in nonerythroid cells (21)(22)(23), a broad list of candidate genes was identified (Dataset S1). Due to the large number of potential binding partners in erythroid cells, additional studies were performed upon both mRNA and protein expression levels of IGF2BP1-binding partners.…”

Section: Igf2bp1 Overexpression Reverses Adult Erythroblasts To a Mormentioning

confidence: 96%

IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts

Vasconcellos

Tumburu

Byrnes

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Here we investigated in primary human erythroid tissues a downstream element of the heterochronic let-7 miRNA pathway, the insulinlike growth factor 2 mRNA-binding protein 1 (IGF2BP1), for its potential to affect the hemoglobin profiles in human erythroblasts. Comparison of adult bone marrow to fetal liver lysates demonstrated developmental silencing in IGF2BP1. Erythroid-specific overexpression of IGF2BP1 caused a nearly complete and pancellular reversal of the adult pattern of hemoglobin expression toward a more fetal-like phenotype. The reprogramming of hemoglobin expression was achieved at the transcriptional level by increased gamma-globin combined with decreased beta-globin transcripts resulting in gamma-globin rising to 90% of total beta-like mRNA. Delta-globin mRNA was reduced to barely detectable levels. Alpha-globin levels were not significantly changed. Fetal hemoglobin achieved levels of 68.6 ± 3.9% in the IGF2BP1 overexpression samples compared with 5.0 ± 1.8% in donor matched transduction controls. In part, these changes were mediated by reduced protein expression of the transcription factor BCL11A. mRNA stability and polysome studies suggest IGF2BP1 mediates posttranscriptional loss of BCL11A. These results suggest a mechanism for chronoregulation of fetal and adult hemoglobin expression in humans.IGF2BP1 | IMP1 | let-7 targets | fetal hemoglobin | ontogeny

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Section: Igf2bp1 Overexpression Reverses Adult Erythroblasts To a Mormentioning

confidence: 96%

IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts

Vasconcellos

Tumburu

Byrnes

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…2. Compared with the entire collection of probe sets on the chip (Jonson et al 2007), where about 10% of all encoded proteins may be connected to cell cycle control and apoptosis, we noted that 21% of the differentially expressed mRNAs in FCs encoded proteins categorized under Figure 1 Results obtained from the PCA done on 92 different thyroid samples based on the entire transcriptome (all genes on the array). Each dot represents a sample that is colored according to the histological grouping.…”

Section: Differentially Expressed Transcriptsmentioning

confidence: 99%

Molecular signatures of thyroid follicular neoplasia

Borup¹,

Rossing²,

Henao³

et al. 2010

Endocrine-Related Cancer

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The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid carcinoma (FC) and normofollicular adenoma (FA) as well as fetal/microFA (fetal adenoma). Carcinomas were strongly enriched in transcripts encoding proteins involved in DNA replication and mitosis corresponding to increased number of proliferating cells and depleted number of transcripts encoding factors involved in growth arrest and apoptosis. In the latter group, the combined loss of transcripts encoding the nuclear orphan receptors NR4A1 and NR4A3, which were recently shown to play a causal role in hematopoetic neoplasia, was noteworthy. The analysis of differentially expressed transcripts provided a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules originating from different geographical locations and platforms with similar accuracy. We came to the conclusion that down-regulation of factors involved in growth arrest and apoptosis may represent a decisive step in the pathogenesis of FC. Moreover, the described molecular pathways provide an accurate and robust genetic signature for the diagnosis of FA and FC.

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“…This protein was previously shown to interact with the DNA-PK-Ku complex 42 and to be part of a ribonucleoprotein assembly containing heterogeneous nuclear ribonucleoproteins (hnRNPs), the heat shock protein HSPA8, the poly-A binding protein PABC1, nucleolin (NCL), and several ribosomal proteins 43 , all of which were also identified here as components of the NKX3.1 interactome ( Figure 1C,D, Data set 1A). Most of these interactions were also represented in the Reactome network ( Figure 2A).…”

Section: Resultsmentioning

confidence: 64%

Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation

Yang

Chung²,

et al. 2014

F1000Res

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NKX3.1 is a homeobox transcription factor whose function as a prostate tumor suppressor remains insufficiently understood because neither the transcriptional program governed by NKX3.1, nor its interacting proteins have been fully revealed. Using affinity purification and mass spectrometry, we have established an extensive NKX3.1 interactome which contains the DNA repair proteins Ku70, Ku80, and PARP, thus providing a molecular underpinning to previous reports implicating NKX3.1 in DNA repair. Transcriptomic profiling of NKX3.1-negative prostate epithelial cells acutely expressing NKX3.1 revealed a rapid and complex response that is a near mirror image of the gene expression signature of human prostatic intraepithelial neoplasia (PIN). Pathway and network analyses suggested that NKX3.1 actuates a cellular reprogramming toward luminal cell differentiation characterized by suppression of pro-oncogenic c-MYC and interferon-STAT signaling and activation of tumor suppressor pathways. Consistently, ectopic expression of NKX3.1 conferred a growth arrest depending on TNFα and JNK signaling. We propose that the tumor suppressor function of NKX3.1 entails a transcriptional program that maintains the differentiation state of secretory luminal cells and that disruption of NKX3.1 contributes to prostate tumorigenesis by permitting luminal cell de-differentiation potentially augmented by defects in DNA repair.

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Molecular Composition of IMP1 Ribonucleoprotein Granules

Cited by 220 publications

References 58 publications

IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts

IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts

Molecular signatures of thyroid follicular neoplasia

Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation

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