Alternative polyadenylation expands the mRNA isoform repertoire of human CD46
Alternative polyadenylation is a prevalent mechanism regulating mammalian gene expression. While tandem 3′-Untranslated-Region (3′UTR) polyadenylation changes expression levels, Intronic PolyAdenylation generates shorter transcripts encoding truncated proteins. Intronic PolyAdenylation regulates 20%...
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sg-ntu-dr.10356-851372023-02-28T16:59:57Z Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 Ly, Phuong Thao Tang, Sze Jing Roca, Xavier School of Biological Sciences Alternative polyadenylation Intronic polyadenylation Alternative polyadenylation is a prevalent mechanism regulating mammalian gene expression. While tandem 3′-Untranslated-Region (3′UTR) polyadenylation changes expression levels, Intronic PolyAdenylation generates shorter transcripts encoding truncated proteins. Intronic PolyAdenylation regulates 20% of genes and is especially common in receptor tyrosine-kinase transcripts, generating soluble repressors. Here we report that human CD46, encoding a TransMembrane repressor of complement and T-cell co-stimulator, expresses multiple isoforms by alternative polyadenylation. We provide evidence for polyadenylation at several introns by RT-PCR of 5′ intronic fragments, and by increase in such isoforms via functional U1 knockdown. We mapped various Intronic PolyAdenylation Sites by 3′ Rapid Amplification of cDNA Ends (3′RACE), which could generate soluble or membrane-bound but tail-less CD46. Intronic PolyAdenylation could add to the source of soluble CD46 isoforms in fluids and tissues, which increase in cancers and autoimmune syndromes. Furthermore, 3′RACE identified three PolyAdenylation Sites within the last intron and exon, whose transcripts with shortened 3′UTRs could support higher CD46 expression. Finally, 3′RACE revealed that the CD46 Pseudogene only expresses short transcripts by early polyadenylation in intron 2. Overall, we report a wide variety of CD46 mRNA isoforms which could generate new protein isoforms, adding to the diverse physiological and pathological roles of CD46. MOE (Min. of Education, S’pore) Accepted version 2017-08-31T03:59:41Z 2019-12-06T15:57:52Z 2017-08-31T03:59:41Z 2019-12-06T15:57:52Z 2017 Journal Article Ly, P. T., Tang, S. J., & Roca, X. (2017). Alternative polyadenylation expands the mRNA isoform repertoire of human CD46. Gene, 625, 21-30. 0378-1119 https://hdl.handle.net/10356/85137 http://hdl.handle.net/10220/43664 10.1016/j.gene.2017.05.004 en Gene © 2017 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Gene, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.gene.2017.05.004]. 24 p. application/pdf |
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Alternative polyadenylation Intronic polyadenylation Ly, Phuong Thao Tang, Sze Jing Roca, Xavier Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 |
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Alternative polyadenylation is a prevalent mechanism regulating mammalian gene expression. While tandem 3′-Untranslated-Region (3′UTR) polyadenylation changes expression levels, Intronic PolyAdenylation generates shorter transcripts encoding truncated proteins. Intronic PolyAdenylation regulates 20% of genes and is especially common in receptor tyrosine-kinase transcripts, generating soluble repressors. Here we report that human CD46, encoding a TransMembrane repressor of complement and T-cell co-stimulator, expresses multiple isoforms by alternative polyadenylation. We provide evidence for polyadenylation at several introns by RT-PCR of 5′ intronic fragments, and by increase in such isoforms via functional U1 knockdown. We mapped various Intronic PolyAdenylation Sites by 3′ Rapid Amplification of cDNA Ends (3′RACE), which could generate soluble or membrane-bound but tail-less CD46. Intronic PolyAdenylation could add to the source of soluble CD46 isoforms in fluids and tissues, which increase in cancers and autoimmune syndromes. Furthermore, 3′RACE identified three PolyAdenylation Sites within the last intron and exon, whose transcripts with shortened 3′UTRs could support higher CD46 expression. Finally, 3′RACE revealed that the CD46 Pseudogene only expresses short transcripts by early polyadenylation in intron 2. Overall, we report a wide variety of CD46 mRNA isoforms which could generate new protein isoforms, adding to the diverse physiological and pathological roles of CD46. |
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School of Biological Sciences |
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School of Biological Sciences Ly, Phuong Thao Tang, Sze Jing Roca, Xavier |
format |
Article |
author |
Ly, Phuong Thao Tang, Sze Jing Roca, Xavier |
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Ly, Phuong Thao |
title |
Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 |
title_short |
Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 |
title_full |
Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 |
title_fullStr |
Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 |
title_full_unstemmed |
Alternative polyadenylation expands the mRNA isoform repertoire of human CD46 |
title_sort |
alternative polyadenylation expands the mrna isoform repertoire of human cd46 |
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2017 |
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https://hdl.handle.net/10356/85137 http://hdl.handle.net/10220/43664 |
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1759856715099013120 |