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Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export
We previously showed that mRNAs synthesized from three genes that naturally lack introns contain a portion of their coding sequence, known as a cytoplasmic accumulation region (CAR), which is essential for stable accumulation of the intronless mRNAs in the cytoplasm. The CAR in each mRNA is unexpect...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575797/ https://www.ncbi.nlm.nih.gov/pubmed/23275560 http://dx.doi.org/10.1093/nar/gks1314 |
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author | Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin |
author_facet | Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin |
author_sort | Lei, Haixin |
collection | PubMed |
description | We previously showed that mRNAs synthesized from three genes that naturally lack introns contain a portion of their coding sequence, known as a cytoplasmic accumulation region (CAR), which is essential for stable accumulation of the intronless mRNAs in the cytoplasm. The CAR in each mRNA is unexpectedly large, ranging in size from ∼160 to 285 nt. Here, we identified one or more copies of a 10-nt consensus sequence in each CAR. To determine whether this element (designated CAR-E) functions in cytoplasmic accumulation of intronless mRNA, we multimerized the most conserved CAR-E and inserted it upstream of β-globin cDNA, which is normally retained/degraded in the nucleus. Significantly, the tandem CAR-E, but not its antisense counterpart, rescued cytoplasmic accumulation of β-globin cDNA transcripts. Moreover, dinucleotide mutations in the CAR-E abolished this rescue. We show that the CAR-E, but not the mutant CAR-E, associates with components of the TREX mRNA export machinery, the Prp19 complex and U2AF2. Moreover, knockdown of these factors results in nuclear retention of the intronless mRNAs. Together, these data suggest that the CAR-E promotes export of intronless mRNA by sequence-dependent recruitment of the mRNA export machinery. |
format | Online Article Text |
id | pubmed-3575797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35757972013-02-19 Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin Nucleic Acids Res RNA We previously showed that mRNAs synthesized from three genes that naturally lack introns contain a portion of their coding sequence, known as a cytoplasmic accumulation region (CAR), which is essential for stable accumulation of the intronless mRNAs in the cytoplasm. The CAR in each mRNA is unexpectedly large, ranging in size from ∼160 to 285 nt. Here, we identified one or more copies of a 10-nt consensus sequence in each CAR. To determine whether this element (designated CAR-E) functions in cytoplasmic accumulation of intronless mRNA, we multimerized the most conserved CAR-E and inserted it upstream of β-globin cDNA, which is normally retained/degraded in the nucleus. Significantly, the tandem CAR-E, but not its antisense counterpart, rescued cytoplasmic accumulation of β-globin cDNA transcripts. Moreover, dinucleotide mutations in the CAR-E abolished this rescue. We show that the CAR-E, but not the mutant CAR-E, associates with components of the TREX mRNA export machinery, the Prp19 complex and U2AF2. Moreover, knockdown of these factors results in nuclear retention of the intronless mRNAs. Together, these data suggest that the CAR-E promotes export of intronless mRNA by sequence-dependent recruitment of the mRNA export machinery. Oxford University Press 2013-02 2012-12-26 /pmc/articles/PMC3575797/ /pubmed/23275560 http://dx.doi.org/10.1093/nar/gks1314 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | RNA Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export |
title | Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export |
title_full | Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export |
title_fullStr | Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export |
title_full_unstemmed | Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export |
title_short | Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export |
title_sort | evidence that a consensus element found in naturally intronless mrnas promotes mrna export |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575797/ https://www.ncbi.nlm.nih.gov/pubmed/23275560 http://dx.doi.org/10.1093/nar/gks1314 |
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