Posttranscriptional mRNA processing as a mechanism for regulation of human A1 adenosine receptor expression.

Ren, Hongzu; Stiles, Gary L.

doi:10.1073/pnas.91.11.4864

Cited by 45 publications

(36 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The human A 1 -R contains multiple exons in its 5ЈUTR. Several alternative splicing transcripts of A 1 -R were observed by using the RT-PCR technique (Ren and Stiles, 1994a). Similar to the finding reported here, expression of human A 1 -R is also regulated at the translational level by two uAUG codons in exon 4 in a tissue-specific manner (Ren and Stiles, 1994b).…”

Section: Discussionsupporting

confidence: 70%

“…Translational regulation has been implicated in the expression of several G protein-coupled receptors including angiotensin II type 1A receptor (Mori et al, 1996), gonadotropin-releasing hormone receptor (Tsutsumi et al, 1995), and A 1 adenosine receptor (A 1 -R) (Ren and Stiles, 1994a). To date, genes encoding four adenosine receptors have been isolated (Ren and Stiles, 1994b;Jacobson et al, 1995;Chu et al, 1996;Atkinson et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

Lee

Chang

et al. 1999

Journal of Neurochemistry

View full text Add to dashboard Cite

Abstract:The rat A 2A adenosine receptor (A 2A -R) gene contains two promoters, P1 and P2, which produce transcript 1 and transcript 2, respectively. These transcripts differ in the lengths of their 5Ј untranslated regions (5ЈUTR1: 514 bp, initiated from P1; 5ЈUTR2: 221 bp, initiated from P2) but encode the same protein. In the present study, we demonstrate that transcript 2 is present in various tissues at different levels, whereas transcript 1 is found only in the striatum. In the striatum, the level of transcript 2 is ϳ300-fold higher than that of transcript 1. The 5ЈUTR of both transcripts suppresses the expression of A 2A -R and a firefly luciferase reporter gene at the translational level; this suppression is not observed after mutational inactivation of an "out-offrame" upstream AUG codon. Translational suppression by the 5ЈUTR was also confirmed in cells using a bicistronic strategy. Collectively, these data suggest that P2 is the major promoter of the rat A 2A -R gene. The 5ЈUTR of the rat A 2A -R gene exerts an inhibitory effect on translation by an upstream open reading frame. Because the 5ЈUTR of the A 2A -R gene possesses strong interspecies homology, translational suppression may be a general mechanism by which the expression of the A 2A -R gene is regulated.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

Lee

Chang

et al. 1999

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Alternative splicing of sequences within the 5Ј-UTR has been demonstrated to regulate receptor expression at the translational level (27). 5, and 9) and kidney (lanes 2, 6, and 10) tissue and the SK-N-MC cell line (lanes 3, 7, and 11) was reverse transcribed and then amplified using one 5Ј-exon-specific primer and one primer for exon 2.…”

Section: Discussionmentioning

confidence: 99%

Multiple Promoters Regulate Tissue-specific Expression of the Human NPY-Y1 Receptor Gene

Ball

Shine

Herzog

1995

Journal of Biological Chemistry

View full text Add to dashboard Cite

The NPY-Y1 receptor is expressed in many tissues including the brain, heart, placenta, spleen, small intestine, kidney, testis, and aortic smooth muscle (4, 5). In the cardiovascular system, the NPY-Y1 receptor mediates both direct vasoconstriction and the potentiation of other pressor agents such as norepinephrine (6). Administration of Y1 selective agonists also affects appetite and the secretion of luteinizing hormone, suggesting involvement of the NPY-Y1 receptor (7,8). NPY is considered to be the most potent endogenous orexigenic agent known with infusions of NPY into the paraventricular nucleus of rats inducing a sizable and long lasting increase in food intake (9).DNA sequences encoding the NPY-Y1 receptor have been cloned from several species including human, rat, mouse, and Xenopus (10 -13). The human cDNA encodes a protein 384 amino acids in length that is preceded by approximately 200 base pairs (bp) of 5Ј-untranslated region (5Ј-UTR) sequence. Analysis of the genomic structure has determined the presence of a 6.4-kb intron within the 5Ј-UTR as well as a small intron within the coding region. The gene for the receptor has been localized to chromosome 4q(31.3-32) (14).During the analysis of NPY-Y1 receptor cDNAs from a testis cDNA library, a cDNA clone was identified that differed from the previously determined NPY-Y1 receptor sequence at the 5Ј-end of the clone. The two sequences diverged at the point where exon 1 splices onto exon 2. This suggests that two exons are alternatively spliced at this site. Although this has no effect on the protein sequence of the receptor, it does have consequences for the regulation of the gene, as transcription may be under the control of multiple promoters.To determine whether alternative promoters are used in the transcription of the NPY-Y1 receptor gene, cDNA clones were isolated from a range of different cDNA libraries, and the 5Ј sequences of NPY-Y1 mRNA were examined by 5Ј-rapid amplification of cDNA ends (RACE). Alternate 5Ј-exons were identified in the structure of the NPY-Y1 receptor gene, and the selective activation of the different promoters for the NPY-Y1 receptor was investigated by measuring the expression of the various NPY-Y1 transcripts in different cell types. MATERIALS AND METHODScDNA Library Screening-Human cDNA libraries (testis, intestine, kidney (Clontech), lung (Stratagene)) were screened with a 32 P-labeled 0.6-kb fragment (nucleotides 817-1437) of the human NPY-Y1 cDNA. Plasmid or bacteriophage DNA was transferred to nylon membranes (DuPont NEN) and hybridized with the probe in a solution of 5 ϫ SSPE, 5 ϫ Denhardt's, and 0.5% SDS at 65°C for 16 h. Membranes were washed twice in 2 ϫ SSPE, 0.1% SDS at room temperature for 15 min followed by a wash for 15 min at 65°C in 1 ϫ SSPE, 0.1% SDS. The filters were then exposed to x-ray film (Kodak, X-Omat) at Ϫ70°C for 16 h using an intensifying screen. Positive colonies were purified, and DNA was isolated using a standard mini-prep or bacteriophage lysate method (15).Genomic Library Screening-A human p...

show abstract

“…Recently, regulation of human A] receptor levels has been shown by changes in translational effi ciency. Alternative mRNA splice variants with different translational efficiencies were detected with higher receptor levels seen with different splice variants in a tissue-specific manner [4], Regulation of receptor levels by different translational efficiency in alternate splice variants does not result in different mRNA levels. Thus, distinguishing between alternative splicing and mechanisms that re sult in changes in message levels in the devel opmental regulation of A!…”

Section: Introductionmentioning

confidence: 98%

“…Regulation of human Ai receptor levels by changes in translational efficiency has recent ly been reported via alternative mRNA splice variants [4]. Regulation of receptor levels by different translational efficiency in alternate splice variants does not result in different mRNA levels.…”

Section: Ontogeny Of Adenosine Receptor and Message Levelsmentioning

confidence: 99%

Changes in Myocardial A<sub>1</sub> Adenosine Receptor and Message Levels during Fetal Development and Postnatal Maturation

Am²,

Jt³

et al. 1996

Neonatology

View full text Add to dashboard Cite

Previously we have shown myocardial adenosine A₁ receptors are up-regulated during the newborn period. The timing of the increase or the mechanism of the changes are not known. The purpose of the present study was to (1) determine the time course of increased A₁ adenosine receptors during fetal development and (2) determine if A₁ adenosine receptor regulation is secondary to changes in A₁ receptor mRNA levels. A₁ adenosine receptor density was determined in whole hearts from fetal rats at 14 and 19 days’ gestation and from newborn and adult rats using standard receptor-binding techniques. A quantitative PCR assay was developed to measure A₁ adenosine receptor mRNA using total RNA samples from the above ages. A₁ receptor density (fmol receptor/mg protein) increased during late gestation (79 ± 14 and 122 ± 7 in 14 and 19 days’ gestation respectively) peaked during the newborn period (136 ± 12) and decreased in the adult rat (36 ± 5). A₁ receptor message levels (fg message/μg total RNA) changed in parallel to receptor density (7.2 ± 1.7, 15.6 ± 1.8, 19.9 ± 4.3 and 9.9 ± 1.3 in 14 and 19 days’ gestation, newborn and adult respectively). These results provide evidence for transcriptional control of A₁ receptor density and the increased receptor density in the newborn heart supports a possible role for the A₁ receptor in the transition to the extrauterine circulation.

show abstract

Posttranscriptional mRNA processing as a mechanism for regulation of human A1 adenosine receptor expression.

Abstract: The human Al adenosine receptor gene contains six exons with exons 1, 2, 3, 4, and part of 5 representing 5' untranslated regions. Reverse transcription-PCR with exon-

Cited by 45 publications

References 17 publications

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

Multiple Promoters Regulate Tissue-specific Expression of the Human NPY-Y1 Receptor Gene

Changes in Myocardial A<sub>1</sub> Adenosine Receptor and Message Levels during Fetal Development and Postnatal Maturation

Contact Info

Product

Resources

About

Posttranscriptional mRNA processing as a mechanism for regulation of human A1 adenosine receptor expression.

Abstract: The human Al adenosine receptor gene contains six exons with exons 1, 2, 3, 4, and part of 5 representing 5' untranslated regions. Reverse transcription-PCR with exon-

Cited by 45 publications

References 17 publications

The 5' Untranslated Regions of the Rat A2A Adenosine Receptor Gene Function as Negative Translational Regulators

The 5' Untranslated Regions of the Rat A2A Adenosine Receptor Gene Function as Negative Translational Regulators

Multiple Promoters Regulate Tissue-specific Expression of the Human NPY-Y1 Receptor Gene

Changes in Myocardial A<sub>1</sub> Adenosine Receptor and Message Levels during Fetal Development and Postnatal Maturation

Contact Info

Product

Resources

About

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators