Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5589566 | Gene | 2017 | 10 Pages |
Abstract
Alternative polyadenylation is a prevalent mechanism regulating mammalian gene expression. While tandem 3â²-Untranslated-Region (3â²UTR) 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 5â² intronic fragments, and by increase in such isoforms via functional U1 knockdown. We mapped various Intronic PolyAdenylation Sites by 3â² Rapid Amplification of cDNA Ends (3â²RACE), 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, 3â²RACE identified three PolyAdenylation Sites within the last intron and exon, whose transcripts with shortened 3â²UTRs could support higher CD46 expression. Finally, 3â²RACE 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.
Keywords
CCP3′RACE5′SSsnRNPpolyadenylation siteCD46reverse transcription - polymerase chain reactionRTKFBSIPANSDMCPRT-PCRRCAASO3′ untranslated region3′UTRantisense oligonucleotideAlternative polyadenylationSTPregulators of complement activationRTK, Receptor tyrosine kinasesmall nuclear ribonucleoproteinfetal bovine serumtransmembraneUnknownPAScomplement control proteinmembrane cofactor proteinPseudogeneSignal peptideAPA
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Genetics
Authors
Phuong Thao Ly, Sze Jing Tang, Xavier Roca,