The Exon Junction Complex: A Multitasking Guardian of the Transcriptome
Autor: | Tracy L. Johnson, Calvin S. Leung |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
RNA Splicing Cell Computational biology Biology Medical and Health Sciences Article DEAD-box RNA Helicases Transcriptome 03 medical and health sciences Exon 0302 clinical medicine Consensus Sequence RNA Precursors medicine Cryptic Splice Sites Humans RNA Messenger Molecular Biology Cell Nucleus RNA-Binding Proteins Cell Biology Exons Biological Sciences Introns RNA Splice Sites Alternative Splicing Cell nucleus 030104 developmental biology medicine.anatomical_structure Ribonucleoproteins Eukaryotic Initiation Factor-4A RNA splicing Exon junction complex 030217 neurology & neurosurgery HeLa Cells Developmental Biology |
Zdroj: | Molecular cell, vol 72, iss 5 |
ISSN: | 1097-4164 |
Popis: | Productive splicing of human precursor messenger RNAs (pre-mRNAs) requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryptic SS are insufficiently explored. Here, we find that many aberrant exonic SS are efficiently silenced by the exon junction complex (EJC), a multi-protein complex that is deposited on spliced mRNA near the exon-exon junction. Upon depletion of EJC proteins, cryptic SS are de-repressed, leading to the mis-splicing of a broad set of mRNAs. Mechanistically, the EJC-mediated recruitment of the splicing regulator RNPS1 inhibits cryptic 5'SS usage, while the deposition of the EJC core directly masks reconstituted 3'SS, thereby precluding transcript disintegration. Thus, the EJC protects the transcriptome of mammalian cells from inadvertent loss of exonic sequences and safeguards the expression of intact, full-length mRNAs. |
Databáze: | OpenAIRE |
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