Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin
<p>Abstract</p> <p>Background</p> <p>Changes in cellular phenotype result from underlying changes in mRNA transcription and translation. Endothelin-1 stimulates cardiomyocyte hypertrophy with associated changes in mRNA/protein expression and an increase in the rate of p...
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| Format: | Article |
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BMC
2010-05-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/11/343 |
| _version_ | 1811261034945576960 |
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| author | Sugden Peter H Tham El L Cullingford Timothy E Marshall Andrew K Markou Thomais Clerk Angela |
| author_facet | Sugden Peter H Tham El L Cullingford Timothy E Marshall Andrew K Markou Thomais Clerk Angela |
| author_sort | Sugden Peter H |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Changes in cellular phenotype result from underlying changes in mRNA transcription and translation. Endothelin-1 stimulates cardiomyocyte hypertrophy with associated changes in mRNA/protein expression and an increase in the rate of protein synthesis. Insulin also increases the rate of translation but does not promote overt cardiomyocyte hypertrophy. One mechanism of translational regulation is through 5' terminal oligopyrimidine tracts (TOPs) that, in response to growth stimuli, promote mRNA recruitment to polysomes for increased translation. TOP mRNAs include those encoding ribosomal proteins, but the full panoply remains to be established. Here, we used microarrays to compare the effects of endothelin-1 and insulin on the global transcriptome of neonatal rat cardiomyocytes, and on mRNA recruitment to polysomes (i.e. the translatome).</p> <p>Results</p> <p>Globally, endothelin-1 and insulin (1 h) promoted >1.5-fold significant (false discovery rate < 0.05) changes in expression of 341 and 38 RNAs, respectively. For these transcripts with this level of change there was little evidence of translational regulation. However, 1336 and 712 RNAs had >1.25-fold significant changes in expression in total and/or polysomal RNA induced by endothelin-1 or insulin, respectively, of which ~35% of endothelin-1-responsive and ~56% of insulin-responsive transcripts were translationally regulated. Of mRNAs for established proteins recruited to polysomes in response to insulin, 49 were known TOP mRNAs with a further 15 probable/possible TOP mRNAs, but 49 had no identifiable TOP sequences or other consistent features in the 5' untranslated region.</p> <p>Conclusions</p> <p>Endothelin-1, rather than insulin, substantially affects global transcript expression to promote cardiomyocyte hypertrophy. Effects on RNA recruitment to polysomes are subtle, with differential effects of endothelin-1 and insulin on specific transcripts. Furthermore, although insulin promotes recruitment of TOP mRNAs to cardiomyocyte polysomes, not all recruited mRNAs are TOP mRNAs.</p> |
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| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-12T18:57:30Z |
| publishDate | 2010-05-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj.art-3b4f9f5bf94e41279c72dd45c1daf60b2022-12-22T03:20:17ZengBMCBMC Genomics1471-21642010-05-0111134310.1186/1471-2164-11-343Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulinSugden Peter HTham El LCullingford Timothy EMarshall Andrew KMarkou ThomaisClerk Angela<p>Abstract</p> <p>Background</p> <p>Changes in cellular phenotype result from underlying changes in mRNA transcription and translation. Endothelin-1 stimulates cardiomyocyte hypertrophy with associated changes in mRNA/protein expression and an increase in the rate of protein synthesis. Insulin also increases the rate of translation but does not promote overt cardiomyocyte hypertrophy. One mechanism of translational regulation is through 5' terminal oligopyrimidine tracts (TOPs) that, in response to growth stimuli, promote mRNA recruitment to polysomes for increased translation. TOP mRNAs include those encoding ribosomal proteins, but the full panoply remains to be established. Here, we used microarrays to compare the effects of endothelin-1 and insulin on the global transcriptome of neonatal rat cardiomyocytes, and on mRNA recruitment to polysomes (i.e. the translatome).</p> <p>Results</p> <p>Globally, endothelin-1 and insulin (1 h) promoted >1.5-fold significant (false discovery rate < 0.05) changes in expression of 341 and 38 RNAs, respectively. For these transcripts with this level of change there was little evidence of translational regulation. However, 1336 and 712 RNAs had >1.25-fold significant changes in expression in total and/or polysomal RNA induced by endothelin-1 or insulin, respectively, of which ~35% of endothelin-1-responsive and ~56% of insulin-responsive transcripts were translationally regulated. Of mRNAs for established proteins recruited to polysomes in response to insulin, 49 were known TOP mRNAs with a further 15 probable/possible TOP mRNAs, but 49 had no identifiable TOP sequences or other consistent features in the 5' untranslated region.</p> <p>Conclusions</p> <p>Endothelin-1, rather than insulin, substantially affects global transcript expression to promote cardiomyocyte hypertrophy. Effects on RNA recruitment to polysomes are subtle, with differential effects of endothelin-1 and insulin on specific transcripts. Furthermore, although insulin promotes recruitment of TOP mRNAs to cardiomyocyte polysomes, not all recruited mRNAs are TOP mRNAs.</p>http://www.biomedcentral.com/1471-2164/11/343 |
| spellingShingle | Sugden Peter H Tham El L Cullingford Timothy E Marshall Andrew K Markou Thomais Clerk Angela Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin BMC Genomics |
| title | Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin |
| title_full | Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin |
| title_fullStr | Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin |
| title_full_unstemmed | Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin |
| title_short | Regulation of the cardiomyocyte transcriptome <it>vs </it>translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin |
| title_sort | regulation of the cardiomyocyte transcriptome it vs it translatome by endothelin 1 and insulin translational regulation of 5 terminal oligopyrimidine tract top mrnas by insulin |
| url | http://www.biomedcentral.com/1471-2164/11/343 |
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