Incrimination of Heterogeneous Nuclear Ribonucleoprotein E1 (hnRNP-E1) as a Candidate Sensor of Physiological Folate Deficiency

Tang, Ying; Khan, Rehana A.; Zhang, Yonghua; Xiao, Suhong; Wang, Mu; Hansen, Deborah K.; Jayaram, Hiremagalur N.; Antony, Asok

doi:10.1074/jbc.m111.230938

Cited by 27 publications

(47 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of ex vivo models support distinct biochemical functions for Pcbp1 and Pcbp2. For example, Pcbp1 is uniquely capable of regulating epithelial-mesenchymal transitions and stabilizing vascular nitric oxide synthase transcripts (37,42,70), while Pcbp2 specifically controls tumor suppressor genes in chronic myelogenous leukemia, poliovirus translation, and HIV gene expression (39)(40)(41). Thus, our in vivo analysis of embryogenesis is concordant with previous ex vivo studies in demonstrating that Pcbp1 and Pcbp2 play distinct roles in organism function.…”

Section: Discussionsupporting

confidence: 80%

“…This conservation of structure and of binding specificity is paralleled by sets of shared functions that include control over globin gene expression, viral replication, and cell proliferation (15,35,36). More recent work has documented a role for both proteins in intracellular iron transport and as sensors of folate deficiency (37,38). Importantly, current evidence also suggests that these proteins may have acquired a subset of nonredundant functions.…”

mentioning

confidence: 95%

See 1 more Smart Citation

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

Ghanem

Kromer

Silverman

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

f RNA-binding proteins participate in a complex array of posttranscriptional controls essential to cell type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts mammalian embryonic development remains incompletely defined, and the level of functional redundancy among subsets of these proteins remains open to question. The poly(C) binding proteins, PCBPs (␣CPs and hnRNP E proteins), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here, we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos undergo normal development until midgestation (12.5 to 13.5 days postcoitum), at which time they undergo a dramatic loss in viability associated with combined cardiovascular and hematopoietic abnormalities. Mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and nondisruptive defect in initial postpartum weight gain. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and have distinct impacts on embryonic viability and that Pcpb2 has a nonredundant in vivo role in hematopoiesis. These data further provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved an essential function(s) in the mammalian genome. P osttranscriptional control of gene expression plays a major role in eukaryotic cell type specification and organism development. RNA processing and mRNA expression are regulated in the nuclear and cytoplasmic compartments by a complex array of interactions among RNA-binding proteins, noncoding RNAs, and target transcripts (1, 2). Studies have documented the central importance of posttranscriptional controls in the programming of embryonic stem cell differentiation and somatic cell development (3-11). The critical role of posttranscriptional control of gene expression can be most clearly recognized in settings of transcriptional inactivity. For example, transcription is globally silenced in the differentiating erythroblast, and the terminal steps in erythrocyte formation are fully dependent on posttranscriptional controls over mRNA stability and translation (12-14). Studies of posttranscriptional controls in this and other models have relied heavily upon a variety of in vitro experimental platforms to define mechanisms and biochemical pathways. While highly informative, such studies do not address the in vivo relevance and nonredundant functions of RNA-binding proteins in physiologically intact environments.The PCBPs (also known as ␣CPs and heterogeneous ribonucleoprotein [hnRNP] E proteins) are a widely expressed and multifunctional family of RNA-binding proteins (15-19) that bind numerous erythroid and nonerythroid mRNAs (20,21). Studies focused on globin gene expression have revealed that t...

show abstract

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 95%

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

Ghanem

Kromer

Silverman

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Notably, homocysteine appeared to promote interactions between heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) and the 18-base FRα mRNA cis-element to promote the synthesis of FRα under folate-deficient conditions [55]. Additionally, homocysteinylated hnRNP-E1 serves as a master regulator in response to the restoration of nutritional folate deficiency.…”

Section: Biology Of Folate Transporters and Enzymes: Relation With DImentioning

confidence: 98%

Novel insights in folate receptors and transporters: implications for disease and treatment of immune diseases and cancer

Jansen

Peters

2015

Pteridines

View full text Add to dashboard Cite

AbstractFolate receptors and transporters as well as folate enzymes play an essential role in human disease and form important targets for the treatment of immune diseases and cancer. To discuss new developments in this area, every 2 years a multidisciplinary meeting is held, which aims to be an informal forum for fundamental scientists and clinicians. During this meeting, the regulation of folate transporters and folate enzymes is discussed at the level of expression, transcription, translation, post-translational modification, and splicing and enzyme regulation. Importantly, this knowledge is applied and translated into exciting clinical applications by clinicians with various backgrounds, such as surgeons, nephrologists, rheumatologists and oncologists. Moreover, the meeting provides an excellent forum for a scientific interaction between academia and industry.

show abstract

“…PCBP1 as well as several other RNA binding proteins, such as PCBP2, AUF1, hnRNPK, and poly(A)-binding protein (PABP), are constituents of the α-complex that binds to the CRE motif to prevent mRNA degradation (Kiledjian et al, 1997; Chkheidze et al, 1999; Wang et al, 1999; Chaudhury et al, 2010). PCBP1 has been shown to regulate stability of many other mRNAs, such as androgen receptor (Yeap et al, 2002), β-globin (Yu and Russell, 2001), collagens I and III (Thiele et al, 2004), disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI) (Chaudhury et al, 2011), endothelial nitric oxide synthase (Ho et al, 2013), erythropoietin (Czyzyk-Krzeska and Bendixen, 1999), folate receptor (Tang et al, 2011), neurofilament-M (Thyagarajan and Szaro, 2008), renin (Skalweit et al, 2003), and tyrosine hydroxylase (Czyzyk-Krzeska and Beresh, 1996). …”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP)

Hwang

Wagley

Law

et al. 2017

Gene

View full text Add to dashboard Cite

Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3′-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3′-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors. The forskolin treatment also enhanced serine- and tyrosine-phosphorylation of AU-rich element binding protein (AUF1), concurrent with its increased binding to the CRE, and led to an increased interaction of poly A binding protein (PABP) with the CRE and poly(A) sites. AUF1 phosphorylation also led to an increased interaction with PCBP1. These findings suggest that a single co-regulator, PCBP1, plays a crucial role in stabilizing MOR mRNA, and is induced by PKA signaling by conforming to AUF1 and PABP.

show abstract

Incrimination of Heterogeneous Nuclear Ribonucleoprotein E1 (hnRNP-E1) as a Candidate Sensor of Physiological Folate Deficiency

Cited by 27 publications

References 75 publications

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

Novel insights in folate receptors and transporters: implications for disease and treatment of immune diseases and cancer

Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP)

Contact Info

Product

Resources

About