Alternative splicing (AS) and transcription elongation are vital biological processes, and their dysregulation causes multiple diseases, including tumors. However, the coregulatory mechanism of AS and transcription elongation in tumors remains unclear. This study demonstrates a novel AS pattern of tight junction protein 1 (ZO1) regulated by the RNA polymerase II elongation rate in colorectal cancer (CRC). Glioma tumor suppressor candidate region gene 1 (GLTSCR1) decreases the transcription elongation rate of ZO1 to provide a time window for binding of the splicing factor HuR to the specific motif in intron 22 of ZO1 and spliceosome recognition of the weak 3' and 5' splice sites in exon 23 to promote exon 23 inclusion. Since exon 23 inclusion in ZO1 suppresses migration and invasion of CRC cells, our findings suggest a novel potential therapeutic target for CRC.
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| http://dx.doi.org/10.1093/jmcb/mjac009 | DOI Listing |
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