Degradation of splicing factor SRSF3 contributes to progressive liver disease

Small Protein Hidden in lncRNA LOC90024 Promotes “Cancerous” RNA Splicing and Tumorigenesis

“…Among the 38 potential SRSP‐interacting splicing regulators, the interaction with SRSF3 was particularly interesting and was selected for further investigation because SRSF3 is a major splicing factor in AS and has critical roles in the regulation of the premRNA splicing, and dysregulation of SRSF3 contributes to tumorigenesis and progression of several human cancers. [ 12,13 ] We further confirmed that SRSP could interact with SRSF3 (Figure 4C). SRSF3 is an RNA splicing factor and RNA‐binding protein.…”

“…[ 8,9,16,17 ] SRSF3 is a major splicing factor in AS and has critical roles in the regulation of premRNA splicing. [ 12 ] In this study, we provide a novel additional mechanism by which splicing factor SRSF3 recognizes and binds its cis‐RNA elements to regulate AS. We discovered that a small protein SRSP encoded by the lncRNA LOC90024 regulates the recognition and binding of SRSF3 to exon 3 of transcription factor Sp4 , resulting in the inclusion of Sp4 exon 3.…”

Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases

“…Taken together, these studies come to the conclusion that a neddylation-dependent pathway is implicated in liver steatosis and fibrosis mainly via regulating the stability of its substrates, which function as critical regulators in the process of liver steatosis. Revealing the role of neddylation in hepatic lipid metabolism and fibrosis progression may pave the way for a novel therapeutic approach in NAFLD and NASH (65).…”

“…Current researches of noncullin substrates of neddylation uncover that neddylation might participate in additional biological process of cells (41) ( Table 2). On this basis, recent studies have uncovered that neddylation inhibition can repress HBV survival (64), alleviate steatosis (65), reduce liver fibrosis (66), and restrain pro-tumor inflammation (67). Considering the progress that has been made Abbreviations: CLD, chronic liver diseases; MDM2, murine double minute-2; NEDD8, neural precursor cell expressed developmentally downregulated-8; HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; HBx, HBV-encoded X protein; HSC, hepatic stellate cell; NAE, NEDD8-activating enzyme; E2F-1, E2F transcription factor 1; ECM, extracellular matrix; CRL, cullin-RING ligases; VHL, von Hippel-Lindau; RBX, RING box protein-1; SKP, S-phase kinase-associated protein; CDT1, chromatin licensing and DNA replication factor; CDT2, chromatin licensing and DNA replication factor 2; NRF2, nuclear factor erythroid 2-related factor 2; NF-κB, the nuclear factor kappa-light-chain-enhancer of activated B cells; ATF4, activating transcription factor 4; βTrCP, beta-transducin repeat containing protein; DCN1, defective in cullin neddylation 1; ROS, reactive oxygen species; mTORC, mammalian target of rapamycin complex; NASH, nonalcoholic steatohepatitis; NAFLD, nonalcoholic fatty liver disease; TRIM40, tripartite motif containing 40; BCA3, breast cancer-associated protein 3; FBXO11, F-box protein 11; HuR, Hu antigen R; TGFβ-RII, transforming growth factor β type II receptor; AICD, APP intracellular domain; EGFR, epidermal growth factor receptor; BRAP2, BRCA1-associated protein 2; SCF, Skp1, cullin, and Fbox protein; RTK, receptor tyrosine kinase; cccDNA, covalently closed circular DNA; IL-8, interleukin-8; MMP9, matrix metalloproteinase-9; DEPTOR, DEP domain containing mTOR-interacting protein; HIFα, hypoxia-inducible factorα; DCAF, DDB1-CUL4-associated factor; IFNα, interferon-α; ColIα1, collagen type I alpha 1; TGFβ, transforming growth factor; TNFα, tumor necrosis factor α; IL-6, interleukin-6; Cxcl, the chemokine (C-X-C motif) ligand; Ccl, the chemokine (C-C motif) ligand; Ccr, the C-C chemokine receptors; c-Cbl, Casita B-lineage lymphoma; pVHL, Von-Hippel-Lindau protein; DDB1, the damagespecific DNA binding protein 1; SARM, sterile α and HEAT/armadillo-motifcontaining protein; Bax, Bcl-2 associated protein X; CUL, cullin; KC, Kupffer cells; CCl4, carbon tetrachloride; JNK, c-Jun N-terminal kinase; Bcl-2, β-cell lymphoma 2; SMC, the structural maintenance of chromosomes; ETFs, electron transfer flavoproteins; SRSF3, serine-rich splicing factor 3; BDL, bile duct ligation; CCl4, carbon tetrachloride; HSP70, heat shock protein 70; SREBP1c, sterol regulatory element-binding protein 1c; HDM2, human homolog of mouse double minute 2; LKB1, liver kinase B1; AGEs, advanced glycation end products; WIPI2, WD repeat domain, phosphoinositide interacting 2.…”

Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role

“…Specifically, Srsf3 is associated with the cell cycle (Kurokawa et al, 2014), cell proliferation (Ajiro et al, 2016;Jia et al, 2010;Song et al, 2019), apoptosis (Kim et al, 2014), glucose and lipid metabolism (Sen et al, 2013), and other key cellular processes (Howard & Sanford, 2015) in different organs such as the liver (Kumar et al, 2019;Sen et al, 2013), brain (Boutej et al, 2017;Song et al, 2019;Wong et al, 2012), and skeletal muscles (Rawcliffe et al, 2016). Furthermore, two recent articles reported splicing activity for Srsf3 in cardiac models.…”