A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation

Shaw, Gray D.; Kamen, Robert

doi:10.1016/0092-8674(86)90341-7

Cited by 4,013 publications

(2,222 citation statements)

References 49 publications

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“…Although the functional implication of CTLA4 polymorphisms in autoimmune diseases is not well established, the (AT) n polymorphism located at the 3 0 end untranslated region has been related to mRNA stability, especially that of cytokine genes, 24 and polymorphisms within the promoter and first exon of the CTLA4 gene have been suggested to be related to the expression levels of CTLA4 molecules. 25 The present analysis confirms the implication of the CTLA4 gene region (locus IDDM12) with T1D.…”

Section: Discussionmentioning

confidence: 99%

Association of the CTLA4 promoter region (−1661G allele) with type 1 diabetes in the South Moroccan population

et al. 2003

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The contribution of the candidate gene CTLA4 to type 1 diabetes is not well established. Although several polymorphisms have been repeatedly associated to the disease, several studies have not confirmed the association. The joint analysis of three SNPs in the CTLA4 promoter region (À1722, À1661, and À319), one SNP in the first exon (+49), and one dinucleotide repeat in the 3 0 untranslated region, in a case-control study in a North African population, shows a strong association of the CTLA4 region with the disease. The À1661G allele showed a significant association with an odds ratio of 2.13. Moreover, the internal structure of the dinucleotide repeat has been deeply analyzed. The present results reveal the importance of polymorphisms in the CTLA4 promoter region, their probable role in gene expression and, ultimately, their relation to the etiology of type 1 diabetes. Previous contradictory association studies might be due to the effect of linkage disequilibrium between the polymorphism analyzed and the alteration within the CTLA4 region. This alteration may be different depending on the genetic background of the population. The present work stresses the need to perform exhaustive analysis of the promoter region polymorphisms in order to detect association with the disease.

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Section: Discussionmentioning

confidence: 99%

Association of the CTLA4 promoter region (−1661G allele) with type 1 diabetes in the South Moroccan population

et al. 2003

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“…Cloning AREs into the 3 UTR of a mammalian reporter transcript triggers rapid degradation (Cok et al, 2003;Fan and Steitz, 1998;Shaw and Kamen, 1986). Additionally, AREs can play a role in the translational efficiency of target mRNAs (Piecyk et al, 2000;Zhang et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The human c‐fos and TNFα AU‐rich elements show different effects on mRNA abundance and protein expression depending on the reporter in the yeast Pichia pastoris

Lautz

Ståhl

Lang

2009

Yeast

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AU-rich elements (AREs) are located in the 3 untranslated region (3 UTR) of their host genes and tightly regulate mRNA degradation and expression. Examples for this kind of regulation are the human proto-oncogene c-fos and the cytokine TNFα. Despite large effort in this field, the exact mechanism of ARE-mediated mRNA turnover remains unclear. In this work we analysed the effects of c-fos-and TNFα AREs on mRNA abundance and protein expression of selected human cDNAs in the yeast Pichia pastoris. This yeast is exceedingly well known for its excellent protein production capacity; however, ARE-like mechanisms have not been studied in this yeast to date. Interestingly, we observed both stabilizing and destabilizing effects of the c-fos ARE, whereas the TNFα ARE has a destabilizing or expression-reducing function in all tested cDNAs. Based on this observation, we introduced a number of single-point mutations upstream of the introduced c-fos ARE into the 3 UTR of a single cDNA in order to demonstrate the importance of ARE-flanking sequences for their own regulation. In conclusion, we illustrate that the analysis of ARE-mediated effects on mRNA abundance and protein expression of a reporter depends on the sequence of the reporter itself as well as the ARE-surrounding sequences within the 3 UTR. For this reason, we question whether already established reporter constructs in other cellular systems display the true type of regulation of the tested AREs for its original host gene. Finally, we propose that AREs should be analysed in their native sequence context.

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“…The longest open reading frame commences at nucleotide 7 and terminates at nucleotide 1518, encoding a putative 503 amino acid polypeptide. Its 3 0 UTR contains a polyadenylation signal AATAAA at nucleotide positions 1752e1757 by polyadq software (http://rulai.cshl.edu/ tools/polyadq/polyadq_form.html) [26], and two putative ATTTA instability sequences, a motif possibly involved in rapid message degradation [27]. Blastp analysis indicated that the translated sequence has significant homology to previously characterized PKR-like proteins of eukaryotic origin.…”

Section: Characterization Of Grpkz Mrna and The Encoded Proteinmentioning

confidence: 99%

Molecular cloning, characterization and expression analysis of the PKZ gene in rare minnow Gobiocypris rarus

Zhu

Wang

2008

Fish & Shellfish Immunology

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A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation

Cited by 4,013 publications

References 49 publications

Association of the CTLA4 promoter region (−1661G allele) with type 1 diabetes in the South Moroccan population

Association of the CTLA4 promoter region (−1661G allele) with type 1 diabetes in the South Moroccan population

The human c‐fos and TNFα AU‐rich elements show different effects on mRNA abundance and protein expression depending on the reporter in the yeast Pichia pastoris

Molecular cloning, characterization and expression analysis of the PKZ gene in rare minnow Gobiocypris rarus

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