Vasopressin mRNA localization in nerve cells: Characterization of cis-acting elements and trans-acting factors

Mohr, Evita; Prakash, Nilima; Vieluf, K; Fuhrmann, Carola; Buck, Friedrich; Richter, Dietmar

doi:10.1073/pnas.111146598

Cited by 35 publications

(31 citation statements)

References 39 publications

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“…PABP is one example of a protein that is currently believed to perform two opposing functions of translational control. In addition to its well-studied role as a translational activator, PABP can mediate translational repression, e.g., of Vasopressin mRNA although the exact mechanism remains unclear (Mohr et al 2001). Dual roles in activation and repression are also suggested by the observation that reduced or elevated levels of PABP have similar effects at the Drosophila neuromuscular junction (NMJ) (Sigrist et al 2000).…”

Section: Discussionmentioning

confidence: 97%

Genetic Modifiers ofdFMR1Encode RNA Granule Components in Drosophila

Cziko¹,

McCann

Howlett³

et al. 2009

Genetics

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Mechanisms of neuronal mRNA localization and translation are of considerable biological interest. Spatially regulated mRNA translation contributes to cell-fate decisions and axon guidance during development, as well as to long-term synaptic plasticity in adulthood. The Fragile-X Mental Retardation protein (FMRP/dFMR1) is one of the best-studied neuronal translational control molecules and here we describe the identification and early characterization of proteins likely to function in the dFMR1 pathway. Induction of the dFMR1 in sevenless-expressing cells of the Drosophila eye causes a disorganized (rough) eye through a mechanism that requires residues necessary for dFMR1/FMRP's translational repressor function. Several mutations in dco, orb2, pAbp, rm62, and smD3 genes dominantly suppress the sev-dfmr1 rough-eye phenotype, suggesting that they are required for dFMR1-mediated processes. The encoded proteins localize to dFMR1-containing neuronal mRNPs in neurites of cultured neurons, and/or have an effect on dendritic branching predicted for bona fide neuronal translational repressors. Genetic mosaic analyses indicate that dco, orb2, rm62, smD3, and dfmr1 are dispensable for translational repression of hid, a microRNA target gene, known to be repressed in wing discs by the bantam miRNA. Thus, the encoded proteins may function as miRNA-and/or mRNA-specific translational regulators in vivo.

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Section: Discussionmentioning

confidence: 97%

Genetic Modifiers ofdFMR1Encode RNA Granule Components in Drosophila

Cziko¹,

McCann

Howlett³

et al. 2009

Genetics

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“…8A). One of these is in the NH 2 terminus (residues [17][18][19][20][21][22][23][24][25][26][27][28][29][30], and the other is nearer to the COOH-terminal end of the protein (residues 345-358) (Fig. 8, A and B).…”

Section: Discussionmentioning

confidence: 99%

“…The 3Ј-UTR of the vasopressin mRNA contains sequences responsible for localizing it to dendrites, termed the "dendritic localizer sequence" (19). Recently, the dendritic localizer sequence has been shown to bind to the multifunctional RNA-binding protein poly(A)-binding protein 1 (PABP1), indicating that this protein may have a role in the polarized delivery of mRNA (21).…”

mentioning

confidence: 99%

Paxillin Associates with Poly(A)-binding Protein 1 at the Dense Endoplasmic Reticulum and the Leading Edge of Migrating Cells

Woods¹,

Roberts²,

Choudhary³

et al. 2002

Journal of Biological Chemistry

125

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“…Because PABP can also bind to poly(G) in vitro (37) and is known to bind a GC-rich region of vasopressin mRNA (12), PABP may bind to the GC-rich region at the 3Ј-UTR of MKK-2 mRNA when its cellular level exceeds a threshold level. The binding of PABP to the GC-rich region of MKK-2 mRNA region may promote the assembly of an mRNA decay complex (48) and/or decrease the residency time of PABP on the 3Ј-poly(A) tail to allow degradation from the 3Ј-end (13).…”

Section: Discussionmentioning

confidence: 99%

Reduced Stability of Mitogen-activated Protein Kinase Kinase-2 mRNA and Phosphorylation of Poly(A)-binding Protein (PABP) in Cells Overexpressing PABP

Musa

Bag

2006

Journal of Biological Chemistry

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The poly(A)-binding protein (PABP) is an important regulator of mRNA translation and stability. The cellular level of PABP is controlled by regulating its mRNA translation by a feedback mechanism. The important aspect of this mechanism is that PABP binds to an adenosine-rich cis-element at the 5-untranslated region of its own mRNA and inhibits its translation. To assess the importance of controlling the PABP level, we studied the effect of PABP overexpression on the transcription profile using the microarray technique. In PABP-overexpressing cells, 19 mRNAs showed a reduction in cellular levels due to reduced mRNA stability, and one showed an increase due to increased mRNA stability. Among these mRNAs, the MKK-2 mRNA encodes the protein kinase activator of ERK1/2 kinase, which is involved in the phosphorylation of eukaryotic initiation factor (eIF) 4E. As a result, mRNA translation may be regulated by the cellular level of MKK-2. In this study, we show that the abundance of the MKK-2 polypeptide is reduced in PABP-overexpressing cells. In these cells, the levels of phosphorylated PABP, eIF4E, and ERK2 are also reduced. Treatment of HeLa cells with the MKK-2 inhibitor U0126 reduced PABP phosphorylation, suggesting that the phosphorylation of PABP is mediated by the MKK-2/ ERK signaling pathway. Thus, a novel signaling pathway involving MKK-2 and ERK1/2 may down-regulate the activity of PABP and eIF4E by controlling their phosphorylation and compensates for the effect of excess cellular PABP.Regulation of the rate of protein synthesis is important for the control of cellular growth and differentiation. Cells respond to changes in growth conditions by fine-tuning the rate of mRNA translation. Initiation of mRNA translation is the rate-limiting step and is often regulated by controlling the interaction between the 5Ј-cap of the mRNA and several initiation factors, including eukaryotic initiation factor (eIF) 2 4E, eIF4G, and eIF4A (1). A recent study has shown that the poly(A)-binding protein (PABP) also behaves like a genuine initiation factor because depletion of PABP from a cell-free extract prevents initiation of mRNA translation (2). The 3Ј-poly(A) tail-bound PABP interacts with eIF4G and circularizes the translating mRNA. This process is believed to enhance mRNA translation by promoting recirculation of terminating ribosomal subunits from the 3Ј-end of the mRNA for another round of initiation (3-6). Although this model is widely accepted, it has not been proven to occur in vivo. In addition, if PABP is essential for mRNA translation, it is possible that PABP participates in mRNA translation by a yet unknown mechanism, as the presence of 3Ј-poly(A) (and thus circularization of mRNA) is not essential for translation initiation of capped mRNAs (7,8).PABP binds to the 3Ј-poly(A) track of eukaryotic mRNA. It also interacts with polypeptides involved in regulating the translation and stability of mRNA (9 -12). Among the four highly conserved RNA-binding domains of PABP, the first two show specificity toward poly(A),...

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Vasopressin mRNA localization in nerve cells: Characterization of cis-acting elements and trans-acting factors

Cited by 35 publications

References 39 publications

Genetic Modifiers ofdFMR1Encode RNA Granule Components in Drosophila

Genetic Modifiers ofdFMR1Encode RNA Granule Components in Drosophila

Paxillin Associates with Poly(A)-binding Protein 1 at the Dense Endoplasmic Reticulum and the Leading Edge of Migrating Cells

Reduced Stability of Mitogen-activated Protein Kinase Kinase-2 mRNA and Phosphorylation of Poly(A)-binding Protein (PABP) in Cells Overexpressing PABP

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