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...

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Main Authors:	Lei, Haixin, Zhai, Bo, Yin, Shanye, Gygi, Steve, Reed, Robin
Format:	Online
Language:	English
Published:	Oxford University Press 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575797/

id	pubmed-3575797
recordtype	oai_dc
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 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin
spellingShingle	Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export
author_facet	Lei, Haixin Zhai, Bo Yin, Shanye Gygi, Steve Reed, Robin
author_sort	Lei, Haixin
title	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_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_sort	evidence that a consensus element found in naturally intronless mrnas promotes mrna export
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.
publisher	Oxford University Press
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575797/
_version_	1611955938948808704

Evidence that a consensus element found in naturally intronless mRNAs promotes mRNA export

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