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IBTK Differently Modulates Gene Expression and RNA Splicing in HeLa and K562 Cells
- Source :
- International Journal of Molecular Sciences, Vol 17, Iss 11, p 1848 (2016), International Journal of Molecular Sciences, International Journal of Molecular Sciences; Volume 17; Issue 11; Pages: 1848
- Publication Year :
- 2016
- Publisher :
- MDPI AG, 2016.
-
Abstract
- The IBTK gene encodes the major protein isoform IBTKα that was recently characterized as substrate receptor of Cul3-dependent E3 ligase, regulating ubiquitination coupled to proteasomal degradation of Pdcd4, an inhibitor of translation. Due to the presence of Ankyrin-BTB-RCC1 domains that mediate several protein-protein interactions, IBTKα could exert expanded regulatory roles, including interaction with transcription regulators. To verify the effects of IBTKα on gene expression, we analyzed HeLa and K562 cell transcriptomes by RNA-Sequencing before and after IBTK knock-down by shRNA transduction. In HeLa cells, 1285 (2.03%) of 63,128 mapped transcripts were differentially expressed in IBTK-shRNA-transduced cells, as compared to cells treated with control-shRNA, with 587 upregulated (45.7%) and 698 downregulated (54.3%) RNAs. In K562 cells, 1959 (3.1%) of 63128 mapped RNAs were differentially expressed in IBTK-shRNA-transduced cells, including 1053 upregulated (53.7%) and 906 downregulated (46.3%). Only 137 transcripts (0.22%) were commonly deregulated by IBTK silencing in both HeLa and K562 cells, indicating that most IBTKα effects on gene expression are cell type-specific. Based on gene ontology classification, the genes responsive to IBTK are involved in different biological processes, including in particular chromatin and nucleosomal organization, gene expression regulation, and cellular traffic and migration. In addition, IBTK RNA interference affected RNA maturation in both cell lines, as shown by the evidence of alternative 3′- and 5′-splicing, mutually exclusive exons, retained introns, and skipped exons. Altogether, these results indicate that IBTK differently modulates gene expression and RNA splicing in HeLa and K562 cells, demonstrating a novel biological role of this protein.
- Subjects :
- 0301 basic medicine
Next Generation Sequencing
lcsh:Chemistry
Exon
Cul3-dependent E3 ligase
IBTK
Next generation sequencing
Transcription
Catalysis
Molecular Biology
Computer Science Applications1707 Computer Vision and Pattern Recognition
Spectroscopy
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry
RNA interference
Transcription (biology)
Cell Movement
Gene expression
transcription
RNA, Small Interfering
lcsh:QH301-705.5
Regulation of gene expression
Intracellular Signaling Peptides and Proteins
RNA-Binding Proteins
General Medicine
Cullin Proteins
Computer Science Applications
Nucleosomes
Organ Specificity
RNA splicing
Signal Transduction
Proteasome Endopeptidase Complex
Ubiquitin-Protein Ligases
Biology
Article
03 medical and health sciences
Protein Domains
Humans
Gene
Adaptor Proteins, Signal Transducing
Intron
Biological Transport
Molecular biology
Alternative Splicing
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Protein Biosynthesis
Proteolysis
Apoptosis Regulatory Proteins
Carrier Proteins
K562 Cells
Transcriptome
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 17
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....708093a02df473d0b96a7cb00e60941e