The Exon Junction Complex Controls the Efficient and Faithful Splicing of a Subset of Transcripts Involved in Mitotic Cell-Cycle Progression

Int J Mol Sci. 2016 Aug 2;17(8):1153. doi: 10.3390/ijms17081153.

Abstract

The exon junction complex (EJC) that is deposited onto spliced mRNAs upstream of exon-exon junctions plays important roles in multiple post-splicing gene expression events, such as mRNA export, surveillance, localization, and translation. However, a direct role for the human EJC in pre-mRNA splicing has not been fully understood. Using HeLa cells, we depleted one of the EJC core components, Y14, and the resulting transcriptome was analyzed by deep sequencing (RNA-Seq) and confirmed by RT-PCR. We found that Y14 is required for efficient and faithful splicing of a group of transcripts that is enriched in short intron-containing genes involved in mitotic cell-cycle progression. Tethering of EJC core components (Y14, eIF4AIII or MAGOH) to a model reporter pre-mRNA harboring a short intron showed that these core components are prerequisites for the splicing activation. Taken together, we conclude that the EJC core assembled on pre-mRNA is critical for efficient and faithful splicing of a specific subset of short introns in mitotic cell cycle-related genes.

Keywords: Y14; exon junction complex (EJC); mitotic cell-cycle; pre-mRNA splicing.

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Exons / genetics*
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Introns / genetics
  • Mitosis / genetics*
  • Models, Genetic
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Cell Cycle Proteins
  • RNA Precursors
  • RNA, Messenger