Drak2 Aggravates Nonalcoholic Fatty Liver Disease Progression Through SRSF6-Associated RNA Alternative Splicing

RNA-binding proteins in metabolic-associated fatty liver disease (MAFLD): From mechanism to therapy

“…Based on one research finding, the rapid degradation of chemokine (C-C motif) ligand 2 (CCL2) mRNA is mediated by GMD during can influence the AS modes of many pre-mRNAs (26). Another case in point is that a lower expression of liver splicing factor serine and arginine rich splicing factor 6 in the mice models of MAFLD and NASH can contribute to disorder of RNA splicing, thus worsening MAFLD (27). Nucleotin is a multifunctional RBP, relocation on the cell membrane and overexpression of which have been verified to bring about cancers of different tissue origins (28).…”

SRSF6 balances mitochondrial-driven innate immune outcomes through alternative splicing of BAX

“…SRSF6 activity is at least in part controlled via phosphorylation by the dual specificity kinases CLK1 and DYRK1a (Hara et al, 2013; Yin et al, 2012), which activates SRSF6 shuttling between the cytoplasm and the nucleus (Sapra et al, 2009). SRSF6 abundance has been repeatedly associated with cancer, liver disease, and diabetes (Jensen et al, 2014; Juan-Mateu et al, 2018; Li et al, 2021) and recent work has identified several roles for SRSF6 in mitochondrial function and cell death. For example, loss of SRSF6 decreases mitochondrial respiration, leading to increased cellular apoptosis in human endoC-BH1 endothelial cells, likely via alternative splicing of cell death factors like Bim , Bax , Diablo , and Bclaf1 (Juan-Mateu et al, 2018).…”

“…Likewise, phosphorylation of SRSF6 induces alternative splicing of mitochondria related genes (e.g. Polg2 , Nudt13 , Guf1 , RnaseI , Nme4 ) in a mouse model of fatty liver disease as well as in human hepatitis patients (Li et al, 2021).…”