Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma
- Faculdade de Medicina da Universidade de Lisboa, Portugal
Figures
Figure 1
Transcription read-through is prevalent in ccRCC.
(A) Top graph depicts the number of genes with transcription read-through per ccRCC sample. The heatmap illustrates the genes with (blue) and without (grey) transcription read-through. The left …
Figure 2
Transcription read-through correlates with ccRCC survival rates.
(A) The top graph indicates the number of genes with transcription read-through on each ccRCC patient sample. Samples were split in two groups according to the number of genes with transcription …
Figure 3 with 3 supplements
SETD2 mutations promote transcription read-through in ccRCC.
(A) SETD2 expression levels (FPKMs) in HEK293 and ccRCC cell lines. (B) Number of genes with transcription read-through up to 4 Kb downstream the TTS. *p<0.05 by Fisher’s Exact Test after comparing …
Figure 3—figure supplement 1
SETD2 mutations in ccRCC cells promote transcription read-through.
Heatmap and metagene of RNA-seq profiles for the following SETD2 mutant ccRCC cell lines: MF (A), AB (B) and ER (C). Heatmap representation of RNA-seq profile distribution and fold change after the …
Figure 3—figure supplement 2
SETD2-depletion impairs transcription termination.
(A,B) Heatmap representation of RNA-seq profile distribution and fold change after the TTS region of genes showing transcription read-through. The left panel shows the read counts (log2 RPKMs) of …
Figure 3—figure supplement 3
SETD2-depletion impairs transcription termination in ccRCC cells.
Caki2 cells were transfected with siRNA oligos against SETD2 or the firefly luciferase (GL2) (control) 48 hr before RNA extraction. RT-qPCR was carried out with primers designed to detect …
Figure 4
SETD2 rescues the transcription termination defects of SETD2 mutant ccRCC cells.
(A) RNA FISH experiments on a SETD2-mutant ccRCC cell line (FG2) transiently expressing wt SETD2-GFP. Quasar570-labeled probes were designed against a region downstream the termination sites of MRPL2…
Figure 5
Transcription read-through overruns and interferes with the expression of neighbouring genes.
Heatmap (A) and metagene (B) profiles of the intergenic region and of the gene located downstream of a read-through event in one representative ccRCC TCGA sample (patient barcode TCGA-CZ-5465). …
Figure 6
Transcription read-through of the KDSR gene correlates with the expression of the BCL2 oncogene.
(A) Distribution of the correlation between the read-through and the expression levels of the downstream tandem genes. Significant correlation values (Benjamini-Hochberg adjusted p<0.05) are …
Figure 7
Read-through RNA chimeras are prevalent in ccRCC.
(A) Circos plots showing the location of genes forming each RNA chimera detected on human ccRCC cell lines and TCGA samples. Chimeras are represented by curves inside the Circos. (B) Number of …
Figure 8
The CTSC-RAB38 chimera is recurrently detected in ccRCC.
(A) Schematic illustration of the CTSC-RAB38 locus depicting the position of the primers used to measure the transcripts levels by RT-qPCR shown in (B) and (C) and the position of the siRNAs …
Additional files
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Supplementary file 1
(A) Genes with transcription read-through identified in human ccRCC TCGA samples. (B) Genes involved in transcription termination and pre-mRNA processing with mutations in TCGA samples. (C) Genes with transcription read-through identified in human ccRCC cell lines. (D) Genes with transcription read-through identified in human 786-O ccRCC cells. (E) Genes with transcription read-through identified in human mesenchymal stem cells. (F) Genes with transcription read-through identified in mouse embryonic stem cells. (G) Genes with transcription read-through identified in human ccRCC TCGA samples, showing significant correlation between read-through levels and expression of downstream gene. (H). Read-Through RNA chimeras identified in human ccRCC TCGA samples and ccRCC cell lines. (I). siRNAs and Primer Sequences. (J) Sequences of RNA FISH probes.
- https://doi.org/10.7554/eLife.09214.014
