PT  - JOURNAL ARTICLE
AU  - Eudenbach, Matthias
AU  - Busam, Jonas
AU  - Bouchard, Caroline
AU  - Rossbach, Oliver
AU  - Zarnack, Kathi
AU  - Bauer, Uta-Maria
TI  - Assessment of PRMT6-dependent alternative splicing in pluripotent and differentiating NT2/D1 cells
AID  - 10.26508/lsa.202402946
DP  - 2025 Apr 01
TA  - Life Science Alliance
PG  - e202402946
VI  - 8
IP  - 4
4099  - http://www.life-science-alliance.org/content/8/4/e202402946.short
4100  - http://www.life-science-alliance.org/content/8/4/e202402946.full
SO  - Life Sci. Alliance2025 Apr 01; 8
AB  - Protein arginine methyltransferase 6 (PRMT6) is a well-characterized epigenetic regulator that methylates histone H3 at arginine 2 (H3R2me2a) in both promoter and enhancer regions, thereby modulating transcriptional initiation. We report here that PRMT6 also regulates gene expression at the post-transcriptional level in the neural pluripotent state and during neuronal differentiation of NT2/D1 cells. PRMT6 knockout causes widespread alternative splicing changes in NT2/D1 cells, most frequently cassette exon alterations. Most of the PRMT6-dependent splicing targets are not transcriptionally affected by the enzyme and regulated in an H3R2me2a-independent manner. However, for a small subset of splicing events, the PRMT6-mediated deposition of H3R2me2a overlaps with the splice site, suggesting a potential dual function in both transcriptional and co-/post-transcriptional regulation. The splicing targets of PRMT6 include ribosomal proteins, splicing factors, and chromatin-modifying enzymes such as PRMT4, DNMT3B, and ASH2L, some of which are associated with differentiation decisions. Taken together, our results in NT2/D1 cells show that PRMT6 exerts predominantly H3R2me2a-independent functions in RNA splicing, which may contribute to pluripotency and neuronal identity.RNA-seq (NT2/D1 CT and KO cells) and ChIP-seq data sets are available at the GEO accession number GSE107612 (Bouchard et al, 2018).