Sequential dimerization of human zipcode-binding protein IMP1 on RNA: a cooperative mechanism providing RNP stability

Nielsen, Jacob; Kristensen, Mette Ahm; Willemoës, Martin; Nielsen, Finn Cilius; Christiansen, Jan

doi:10.1093/nar/gkh754

Cited by 115 publications

(148 citation statements)

References 27 publications

(26 reference statements)

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“…IGF2BP1 acts in a tissue-specific manner to regulate the expression of proteins via multiple separate mechanisms, including increased mRNA decay, protein compartmentalization, or translational regulation (33,(39)(40)(41)(42)(43). Because an IGF2BP1-OE vector driven by the erythroid-specific SPTA1 promoter was designed for this study, stem cell reprogramming is not required for its erythroid effects.…”

Section: Bcl11a Is Posttranscriptionally Regulated In Igf2bp1 Overexpmentioning

confidence: 99%

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: Bcl11a Is Posttranscriptionally Regulated In Igf2bp1 Overexpmentioning

confidence: 99%

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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“…Dimerization of proteins that bind to RNA is not unprecedented; for example, the Cys 3 His ZF ZAP is a monomer in solution that then dimerizes upon binding to the ZAP-responsive RNA element (34). Other RNA-binding proteins that recognize their targets in a cooperative manner are the human zipcode-binding protein IMP-1, HIV-1 Rev protein, hordeiviral γb protein, human La protein, and tomato bushy stunt virus p33 protein (35)(36)(37)(38). There are also other AUrich RNA-binding proteins such as AUF-1 (p42), Hsp70, and HuR, which bind to their respective RNA partners in a cooperative manner (39)(40)(41).…”

Section: Cpsf30 Contains Ironmentioning

confidence: 99%

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

Shimberg

Michalek

Oluyadi

et al. 2016

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

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Cleavage and polyadenylation specificity factor 30 (CPSF30) is a key protein involved in pre-mRNA processing. CPSF30 contains five Cys 3 His domains (annotated as "zinc-finger" domains). Using inductively coupled plasma mass spectrometry, X-ray absorption spectroscopy, and UV-visible spectroscopy, we report that CPSF30 is isolated with iron, in addition to zinc. Iron is present in CPSF30 as a 2Fe-2S cluster and uses one of the Cys 3 His domains; 2Fe-2S clusters with a Cys 3 His ligand set are rare and notably have also been identified in MitoNEET, a protein that was also annotated as a zinc finger. These findings support a role for iron in some zinc-finger proteins. Using electrophoretic mobility shift assays and fluorescence anisotropy, we report that CPSF30 selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF30/RNA binding. Removal of zinc, or both zinc and iron, abrogates binding, whereas removal of just iron significantly lessens binding. From these data we propose a model for RNA recognition that involves a metaldependent cooperative binding mechanism.zinc | iron-sulfur | RNA | protein | binding

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“…The Xenopus and human homologs are between 70% and 84% identical across the almost 600 amino acid length of the protein, with the highest regions of conservation in the RNA binding motifs (Zhang et al 1999;Yaniv and Yisraeli 2002). KH domains 3 and 4 have been implicated in mediating not only RNA binding (Git and Standart 2002;Farina et al 2003) but also selfassociation of the protein (Git and Standart 2002;Nielsen et al 2004). In addition, VICKZ proteins appear to associate with a number of other proteins in ribonucleoprotein particles (Moraes et al 2003;Kress et al 2004;Yoon and Mowry 2004;Patel et al 2005).…”

Section: Introductionmentioning

confidence: 99%

VICKZ proteins mediate cell migration via their RNA binding activity

Oberman¹,

Rand²,

Maizels³

et al. 2007

RNA

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The highly conserved, RNA binding VICKZ proteins help regulate RNA localization, stability, and translation in many eukaryotes. These proteins are also required for cell migration in embryos and cultured cells. In adults, many tumors overexpress VICKZ homologs, and it has been hypothesized that the proteins can mediate cell motility and invasion. How these proteins facilitate cell movement and, in particular, whether their ability to bind RNA plays a role in their function remain unclear. Using HPLC and mass spectrometry to identify a region of Xenopus Vg1 RBP (xVICKZ3) that binds the vegetal localization element of Vg1 RNA, we generated a deletion construct that functions in a dominant-negative manner. The construct associates with full-length xVICKZ3 and severely reduces binding to target RNAs. This dominant-negative construct phenocopies the effect of down-regulating xVICKZ3 in Xenopus embryos. A corresponding deletion in the human homolog hVICKZ1 similarly functions in a dominant-negative fashion to reduce the ability of full-length hVICKZ protein to bind RNA. Expression of the dominant-negative construct in human carcinoma cells inhibits cell movement by several criteria. We conclude that the ability of VICKZ proteins to mediate cell migration, in vitro and in vivo, requires their RNA binding activity.

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Sequential dimerization of human zipcode-binding protein IMP1 on RNA: a cooperative mechanism providing RNP stability

Cited by 115 publications

References 27 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

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

VICKZ proteins mediate cell migration via their RNA binding activity

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