Negative Control of the Poly(A)-binding Protein mRNA Translation Is Mediated by the Adenine-rich Region of Its 5′-Untranslated Region

Wu, Jun; Bag, Jnanankur

doi:10.1074/jbc.273.51.34535

Cited by 82 publications

(95 citation statements)

References 42 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While it has been previously established that Paips regulate the activity of PABP (12,16), the mechanism by which PAIP2 modulates the levels of PABP expression has yet to be identified. Although PABP has been show to autoregulate the translation of its own mRNA by binding to an adenine-rich region in its 5′ UTR (17), this mechanism does not appear to counteract the overexpression of Pabp that Yanagiya and colleagues observed in the Paip2a-KO mice (10). Thus, the cause of Pabp upregulation in these animals remains unclear.…”

Section: Paip2a: Both a Repressor And An Activator Of Translationmentioning

confidence: 84%

Too much PABP, too little translation

Kini

Vishnu

Liebhaber³

2010

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

Section: Paip2a: Both a Repressor And An Activator Of Translationmentioning

confidence: 84%

Too much PABP, too little translation

Kini

Vishnu

Liebhaber³

2010

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Plasmids-A PABP cDNA clone (pHu73 plasmid) (35) was digested with BamHI and SacII, which removed the first 263 nucleotides of the PABP cDNA containing the adenosine-rich autoregulatory region and released the cDNA insert from the vector (24). The PABP cDNA fragment was cloned at the AvrII/BamHI sites of the pCMV-SPORT-␤-gal vector (Invitrogen) from which the ␤-galactosidase coding region was removed.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, control of PABP expression may be critical for cellular physiology. Accumulated evidences show that PABP expression is regulated primarily at the post-transcriptional level (21)(22)(23)(24)(25)(26)(27). However, in some instances, transcription of the PABP gene can also be regulated (28).…”

mentioning

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

Self Cite

View full text Add to dashboard Cite

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),...

show abstract

“…In most instances in which an autoregulation of translation has been documented, the autoregulated protein has an RNA binding function that mediates its interaction with its own transcript (Portier et al, 1990;Mosner et al, 1995;Wu and Bag, 1998;Hendrick et al, 2001). Here, we found no evidence for such a direct interaction.…”

Section: A Ternary Effector Is Needed For the Ces Processmentioning

confidence: 99%

CytochromefTranslation in Chlamydomonas Chloroplast Is Autoregulated by its Carboxyl-Terminal Domain[W]

et al. 2003

View full text Add to dashboard Cite

The rate of synthesis of cytochrome f is decreased ‫ف‬ 10-fold when it does not assemble with the other subunits of the cytochrome b 6 f complex in Chlamydomonas reinhardtii chloroplasts. This assembly-mediated regulation of cytochrome f synthesis corresponds to a regulation of petA mRNA initiation of translation. Here, we demonstrate that cytochrome f translation is autoregulated by its C-terminal domain. Five cytochrome f residues conserved throughout all chloroplast genomes-residue Gln-297 in the transmembrane helix and a cluster of four amino acids, Lys-Gln-Phe-Glu, at positions 305 to 308, in the stromal extension-participate in the formation of a translation repressor motif. By contrast, positively charged residues in the stromal extension have little influence on the autoregulation process. These results do not favor a direct interaction between the repressor motif and the petA 5 Ј untranslated region but suggest the participation of a membrane-bound ternary effector.

show abstract

Negative Control of the Poly(A)-binding Protein mRNA Translation Is Mediated by the Adenine-rich Region of Its 5′-Untranslated Region

Cited by 82 publications

References 42 publications

Too much PABP, too little translation

Too much PABP, too little translation

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

CytochromefTranslation in Chlamydomonas Chloroplast Is Autoregulated by its Carboxyl-Terminal Domain[W]

Contact Info

Product

Resources

About