Two ZBP1 KH domains facilitate β-actin mRNA localization, granule formation, and cytoskeletal attachment

Farina, Kim L.; Hüttelmaier, Stefan; Musunuru, Kiran; Darnell, Robert B.; Singer, Robert H.

doi:10.1083/jcb.200206003

Cited by 241 publications

(298 citation 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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“…Another example of a positive regulator is the zipcode binding protein 1 (ZBP1), which mediates actin-dependent localization of ␤-actin mRNA in chicken embryo fibroblasts (CEFs; for review, see Jansen 2001). Predominantly a cytoplasmic protein, ZBP1 binds to a 54-nt cis-acting element or "zipcode" located in the 3Ј UTR of the ␤-actin mRNA and colocalizes with the RNA to the leading lamellae (Farina et al 2003). ZBP1 appears in large cytoplasmic granules, which codistribute with ␤-actin mRNA granules thought to contain components necessary for transport, localization, and translation of specific mRNAs.…”

Section: Mechanism Of Hrip Actionmentioning

confidence: 99%

hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region

Sánchez-Velar

Udofia²,

Yu³

et al. 2003

Genes Dev.

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Human immunodeficiency virus Rev facilitates the cytoplasmic accumulation of viral RNAs that contain aRev binding site. A human Rev-interacting protein (hRIP) was originally identified based on its ability to interact with the Rev nuclear export signal (NES) in yeast two-hybrid assays. To date, however, the function of hRIP and a role for hRIP in Rev-directed RNA export have remained elusive. Here we ablate hRIP activity with a dominant-negative mutant or RNA interference and analyze Rev function by RNA in situ hybridization. We find, unexpectedly, that in the absence of functional hRIP, Rev-directed RNAs mislocalize and aberrantly accumulate at the nuclear periphery, where hRIP is localized. In contrast, in the absence of Rev or the Rev cofactor CRM1, Rev-directed RNAs remain nuclear. We further show that the RNA mislocalization pattern resulting from loss of hRIP activity is highly specific to Rev function: the intracellular distribution of cellular poly(A) + mRNA, nuclear proteins, and, most important, NES-containing proteins, are unaffected. Thus, hRIP is an essential cellular Rev cofactor, which acts at a previously unanticipated step in HIV-1 RNA export: movement of RNAs from the nuclear periphery to the cytoplasm. Animal viruses often encode regulatory proteins, which facilitate expression of their viral genes in the host cell. One such example is the human immunodeficiency virus type 1 (HIV-1) Rev protein, which uses a novel mechanism to regulate viral messenger RNA (mRNA) export from the nucleus. Rev is a sequence-specific RNA binding protein that facilitates the cytoplasmic accumulation of the intron-containing HIV-1 gag-pol and env mRNAs (Cullen 2002). Rev interacts with a cis-acting viral RNA element in these mRNAs designated the Rev responsive element (RRE; Pollard and Malim 1998; Hope 1999). Rev contains two distinct functional domains: an arginine-rich RNA binding motif (ARM) and a leucinerich "effector" domain. Rev's ARM domain confers sequence-specific RNA binding, protein oligomerization, and nuclear targeting (Frankel and Young 1998). Rev's effector domain contains a leucine-rich nuclear export signal (NES), which binds the nuclear export receptor CRM1 (Weis 2002). Other cellular proteins have been shown to interact directly or indirectly with the Rev NES, including the kinesin-like Rev/Rex effector binding protein (REBP) and the eukaryotic initiation factor-5 alpha (eIF-5␣; Bevec et al. 1996;Dayton 1996;Kjems and Askjaer 2000;Venkatesh et al. 2003).The human Rev-interacting protein (hRIP), also known as hRab or Hrb, was identified using a yeast twohybrid screen with Rev as the bait (Bogerd et al. 1995;Fritz et al. 1995). Additional studies demonstrated a strong correlation between the ability of Rev NES mutants to support Rev function in yeast and their ability to interact with hRIP in the two-hybrid assay (Stutz et al. 1996). However, subsequent genetic analyses indicate the Rev-hRIP interaction is indirect, and is likely bridged by CRM1 (Fritz and Green 1996;Henderson and Percipalle 1997;Ne...

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“…To evaluate the role of IMP1 in ovarian carcinomas, phenotypic effects of aberrant IMP1 expression were analysed by small interfering RNA (siRNA)-mediated Immunostaining was performed on paraffin-embedded tissue sections, as described previously (Kobel et al, 2006), using a IMP1 (ZBP1)-directed antibody (Farina et al, 2003;Huttelmaier et al, 2005). Two slides per sample were immunostained together in two runs before the semiquantitative evaluation of the immunoreactivity by a pathologist (MK) blinded to the clinical data.…”

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confidence: 99%

“…In (b), ES-2 cell numbers were determined post-transfection of indicated siRNAs and normalization to cell numbers 24 h post-transfection, set to 100%. The specific knockdown of IMP1 was determined by western blotting of OVCAR-3 and ES-2 cell lysates 72 h post-transfection with anti-vinculin (Sigma, Mu¨nchen, Germany), anti-tubulin (Sigma) and anti-IMP1 (ZBP1) (Farina et al, 2003), as described previously (Huttelmaier et al, 2005). Relative expression levels of indicated genes were determined by quantitative RT-PCR (d).…”

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confidence: 99%

Expression of the RNA-binding protein IMP1 correlates with poor prognosis in ovarian carcinoma

et al. 2007

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The IMP (IGFII mRNA-binding protein) family comprises a group of three RNA-binding proteins involved in the regulation of cytoplasmic mRNA-fate. Recent studies identified IMP proteins as oncofetal factors in various neoplasias, but knowledge of a potential role in ovarian carcinomas is still lacking. The immunohistochemical analysis of 107 ovarian carcinomas, 30 serous borderline tumors of the ovary and five normal ovaries revealed de novo synthesis of IMP1 in 69% of ovarian carcinomas. Elevated IMP1 expression was observed preferentially in high-grade and high-stage cases and was a significant prognostic indicator for reduced recurrence-free and overall survival. Phenotypic studies in ovarian carcinoma-derived ES-2 cells demonstrated that IMP1 knockdown affects proliferation and cell survival. Reduced proliferation was associated with decreased c-myc mRNA half-life, suggesting IMP1 as an oncogenic factor that is involved in promoting elevated proliferation by stabilizing the c-myc mRNA in ovarian carcinoma cells.

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Two ZBP1 KH domains facilitate β-actin mRNA localization, granule formation, and cytoskeletal attachment

Cited by 241 publications

References 50 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

hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region

Expression of the RNA-binding protein IMP1 correlates with poor prognosis in ovarian carcinoma

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