PTBP1 mRNA isoforms and regulation of their translation
- 1Graduate Study in Comparative Biochemistry, University of California, Berkeley, California 94720, USA
- 2Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA
- 3Department of Cell and Tissue Biology, University of California, San Francisco, California 94143, USA
- 4Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA
- 5Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA
- 6Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
- 7California Institute for Quantitative Biosciences 3 (QB3), University of California, Berkeley, Berkeley, California 94720, USA
- Corresponding author: jcate{at}lbl.gov
Abstract
Polypyrimidine tract-binding proteins (PTBPs) are RNA binding proteins that regulate a number of posttranscriptional events. Human PTBP1 transits between the nucleus and cytoplasm and is thought to regulate RNA processes in both. However, information about PTBP1 mRNA isoforms and regulation of PTPB1 expression remains incomplete. Here we mapped the major PTBP1 mRNA isoforms in HEK293T cells and identified alternative 5′ and 3′ untranslated regions (5′-UTRs, 3′-UTRs), as well as alternative splicing patterns in the protein coding region. We also assessed how the observed PTBP1 mRNA isoforms contribute to PTBP1 expression in different phases of the cell cycle. Previously, PTBP1 mRNAs were shown to crosslink to eukaryotic translation initiation factor 3 (eIF3). We find that eIF3 binds differently to each PTBP1 mRNA isoform in a cell cycle dependent manner. We also observe a strong correlation between eIF3 binding to PTBP1 mRNAs and repression of PTBP1 levels during the S phase of the cell cycle. Our results provide evidence of translational regulation of PTBP1 protein levels during the cell cycle, which may affect downstream regulation of alternative splicing and translation mediated by PTBP1 protein isoforms.
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.070193.118.
- Received December 24, 2018.
- Accepted June 26, 2019.
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