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CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204.


ABSTRACT: T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3´ untranslated regions (3´-UTRs) derived from alternative pre-mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T-cell surface glycoprotein that negatively regulates TCR signaling from the onset of T-cell activation. CD5 plays a pivotal role in mediating outcomes of cell survival or apoptosis, and may prevent both autoimmunity and cancer. In human primary T lymphocytes and Jurkat cells we found three distinct mRNA isoforms encoding CD5, each derived from distinct poly(A) signals (PASs). Upon T-cell activation, there is an overall increase in CD5 mRNAs with a specific increase in the relative expression of the shorter isoforms. 3´-UTRs derived from these shorter isoforms confer higher reporter expression in activated T cells relative to the longer isoform. We further show that polypyrimidine tract binding protein (PTB/PTBP1) directly binds to the proximal PAS and PTB siRNA depletion causes a decrease in mRNA derived from this PAS, suggesting an effect on stability or poly(A) site selection to circumvent targeting of the longer CD5 mRNA isoform by miR-204. These mechanisms fine-tune CD5 expression levels and thus ultimately T-cell responses.

SUBMITTER: Domingues RG 

PROVIDER: S-EPMC5555168 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204.

Domingues Rita G RG   Lago-Baldaia Inês I   Pereira-Castro Isabel I   Fachini Joseph M JM   Oliveira Liliana L   Drpic Danica D   Lopes Nair N   Henriques Telmo T   Neilson Joel R JR   Carmo Alexandre M AM   Moreira Alexandra A  

European journal of immunology 20160415 6


T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3´ untranslated regions (3´-UTRs) derived from alternative pre-mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T-cell surface glycoprotein that negatively regulates TCR signaling from the onset of T-cell activation. CD5 plays a pivotal role in mediating outcomes of cell survival or apoptosis, and may prev  ...[more]

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