hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA

Rajagopalan, Lakshman E.; Westmark, Cara J.; Jarzembowski, Jason A.; Malter, James S.

doi:10.1093/nar/26.14.3418

Cited by 110 publications

(89 citation statements)

References 54 publications

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“…The 3' UTR of APP mRNA was found to be a substrate for association by nucleolin, as well as by the RBPs hnRNP C and fragile X mental retardation protein (FMRP). [38][39][40][41] The helicase activity of nucleolin was proposed to accelerate APP mRNA degradation in response to stress, an effect that was counteracted by the stabilizing influence of hnRNP C. 41 IL2 mRNA. Interleukin (IL)-2 is a major cytokine implicated in the response against microbial infection and is used in certain cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein nucleolin in disease

2012

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Section: Introductionmentioning

confidence: 99%

RNA-binding protein nucleolin in disease

2012

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“…At the transcriptional level, nucleolin was shown to be a subunit of a RNA polymerase II complex [43], to stimulate transcription [44] and to have chromatin remodeling activity [9]. Nucleolin is also a polyfunctional RNA-binding factor involved in the stabilization and export of mRNA with several different heterogeneous nuclear ribonucleoproteins (hnRNP) [45][46][47]. Here, the majority of polypeptides that were identified by proteomics (Table 1) have functions in mRNA processing and may bind to nucleolin (i.e.…”

Section: Discussionmentioning

confidence: 99%

Proteomics of RNA polymerase II holoenzymes during P19 cardiomyogenesis

Maës

2007

Open Life Sciences

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Abstract:The embryonal carcinoma P19 model has allowed the elucidation of a role for several transcription factors in cell differentiation. Here, the regulation of the RNA polymerase II machinery has been explored through its association with multifunctional complexes involved in transcription. An interaction proteomics analysis of TFIIS-purified RNA polymerase II (RNAPII) holoenzymes during cardiomyogenesis is described. Modifications of protein complexes that may be associated with transcriptionally active and activator responsive RNAPII holoenzymes were detected in a serum and DMSO dependent manner. Subunits of the PAF1 and Mediator complexes were correlated with holoenzymes from non-differentiated and terminally differentiated P19 cultures respectively. Moreover, high levels of nucleolin were identified in all forms of holoenzymes by two-dimensional gel electrophoresis, and suggest that nucleolin could bind to RNAPII and TFIIS. Several proteins that were identified in the RNAPII holoenzymes are known to have functions in mRNA processing and may bind to nucleolin. A novel function for nucleolin is proposed as a possible pivotal platform between transcription, mRNA processing and export.

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“…In the 5ЈUTR, APP mRNA contains a sequence homologous to the iron-responsive element which modulates translation in response to interleukin 1 stimulation of astrocytoma cells (32). In the 3ЈUTR, a 29-oligonucleotide element (28,45) and an 81-oligonucleotide element (1) have been demonstrated to increase the stability of the APP mRNA through protein-mRNA interactions. These stabilizing elements are located upstream of the regulatory sequence reported here and have no homology with our cis sequence.…”

Section: Discussionmentioning

confidence: 99%

A GG Nucleotide Sequence of the 3′ Untranslated Region of Amyloid Precursor Protein mRNA Plays a Key Role in the Regulation of Translation and the Binding of Proteins

Mbella

Bertrand

Huez

et al. 2000

Molecular and Cellular Biology

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The alternative polyadenylation of the mRNA encoding the amyloid precursor protein (APP) involved in Alzheimer's disease generates two molecules, with the first of these containing 258 additional nucleotides in the 3 untranslated region (3 UTR). We have previously shown that these 258 nucleotides increase the translation of APP mRNA injected in Xenopus oocytes (5). Here, we demonstrate that this mechanism occurs in CHO cells as well. We also present evidence that the 3 UTR containing 8 nucleotides more than the short 3 UTR allows the recovery of an efficiency of translation similar to that of the long 3 UTR. Moreover, the two guanine residues located at the 3 ends of these 8 nucleotides play a key role in the translational control. Using gel retardation mobility shift assay, we show that proteins from Xenopus oocytes, CHO cells, and human brain specifically bind to the short 3 UTR but not to the long one. The two guanine residues involved in the translational control inhibit this specific binding by 65%. These results indicate that there is a correlation between the binding of proteins to the 3 UTR of APP mRNA and the efficiency of mRNA translation, and that a GG motif controls both binding of proteins and translation.The control of gene expression governs cell differentiation. The first step of this control is provided by the transcription of specific genes. In eucaryotic cells, the scanning of a gene by the RNA polymerase II leads to the production of a nuclear transcript which, in most cases, will undergo three major modifications: capping of its 5Ј untranslated region (5ЈUTR), polyadenylation of the 3ЈUTR, and splicing of introns (13,38).At the postranscriptional level, the efficiency of translation of mature mRNA can also regulate gene expression. The phosphorylation of initiation factors of translation, which interact with the 5Ј end of mRNAs, has been demonstrated to modulate translation (21, 31).The presence of secondary structures in the 5ЈUTR can also influence mRNA translation either by increasing the binding affinity of some eucaryotic initiation factors (18) or by interacting with cellular proteins which can completely inhibit the initiation of translation (9,33).Although the 3ЈUTR is located downstream of the coding sequence, it has been widely demonstrated that this region can also modulate mRNA translation (41). The poly(A) tail is one element of the 3ЈUTR implicated in both the stability of mRNA and the regulation of its translation (34). The poly(A) tail can increase the stability of an mRNA molecule by protecting the mRNA from digestion by 3Ј35Ј exonucleases (7). A more dynamic role has been attributed to the poly(A) tail since it was demonstrated that its removal from the 3Ј end of capped mRNA decreases translation (22, 37). In Saccharomyces cerevisiae the enhancement of translation mediated by the poly(A) tail requires the formation of a complex between the poly(A) tail and a poly(A) binding protein (PABP) since the depletion of the PABP results in the inhibition of translation (36). This co...

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hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA

Cited by 110 publications

References 54 publications

RNA-binding protein nucleolin in disease

RNA-binding protein nucleolin in disease

Proteomics of RNA polymerase II holoenzymes during P19 cardiomyogenesis

A GG Nucleotide Sequence of the 3′ Untranslated Region of Amyloid Precursor Protein mRNA Plays a Key Role in the Regulation of Translation and the Binding of Proteins

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