Transcriptomic analysis of HeLa cells depleted in CELF1, ELAVL1, and both

ELAVL1 and CELF1 are two RNA-binding proteins involved in alternative splicing control. To address their functional relationships, we identify the differentially spliced mRNAs upon depletion of CELF1, ELAVL1, or both. These proteins control similar sets of genes with similar consequences on exon inclusion or skipping. The magnitude of the effect of the double depletion equals the sum of the magnitudes of the individual depletions, showing that CELF1 and ELAVL1 additively control their target RNAs. CELF1 and ELAVL1 regulated splicing events include ACSL4, WNK1, CD44, MICAL3, and JDP2. Using FRET, we find that CELF1 and ELAVL1 directly interact in cell nuclei. We demonstrate that the combined levels of CELF1 and ELAVL1 is a valuable biomarker in breast cancer, while their levels bring very limited information when taken individually. A “co-RNA splicing map” of CELF1 and ELAVL1 shows they repress alternative splice sites when bound nearby, but activate them when bound further away. Together, these data point to strong functional interactions between CELF1 and ELAVL1 to control alternative splicing with significant impacts in human pathology. HeLa cells were transfected with mock siRNAs, or siRNAs directed against CELF1, ELAVL1, or both. RNAs were extracted 48h after siRNA transfection. Three independent transfection experiments were carried out for each depletion (II, III, IV). Please note that there are 6 raw files for 12 samples since two samples were on the same array, one in Cy3 and one in Cy5. The corresponding raw data file for each sample is indicated in the Sample description field.