Abstract. SRSF2 (serine/arginine-rich splicing factor 2) is a critical regulator of pre-messenger RNA splicing, which also plays noncanonical functions in

Cancer-associated splicing factor (SF) mutations in SF3B1, U2AF1, and SRSF2 induce distinct changes in alternative splicing (AS). Yet these mutations are strikingly mutually exclusive, pointing to a c...

Abstract. SRSF2 (serine/arginine-rich splicing factor 2) is a critical regulator of pre-messenger RNA splicing, which also plays noncanonical functions in

In Myeloiddysplastic syndromes, CEBPA mutations are linked to disease progression and AML. Here, the authors use somatic reprogramming and genome editing to generate isogenic cell lines from an MDS pa...

<p indent="0mm">Metabolic alterations are a hallmark of cancer, yet their direct influence on oncogenic splicing remains unclear. This study demonstrates that castration-resistant prostate cancer (CRPC) exhibits enhanced glycolysis compared to hormone-sensitive disease, resulting in elevated lactate and increased global protein lactylation. Lactylomic profiling identifies the splicing factor SRSF2 as a key target, modified at a conserved lysine (K36). SRSF2 lactylation competes with ubiquitination, thereby stabilizing the protein and enabling it to promote the alternative splicing of androgen receptor (AR) pre-mRNA into the AR-V7 variant, a major driver of CRPC development. Functional assays confirm that both LDHA and SRSF2 are critical for CRPC cell proliferation, migration, and tumor growth, and their high expression correlates with poor patient prognosis. Our work establishes a direct mechanistic link between glycolysis and oncogenic splicing via protein lactylation,

SRSF2 mutations occur in up to 25% of acute myeloid leukemia (AML) and 17% of myelodysplastic syndrome (MDS) cases and are associated with poor prognosis, yet no mutation-directed therapy exists. Here...

Myelodysplastic syndrome disease (MDS) is caused by the successive acquisition of mutations and thus displays a variable risk for progression to AML. Mutations in CEBPA are commonly associated with a...

Alternative splicing serves as a crucial post-transcriptional regulatory mechanism, enabling a single pre-mRNA transcript to undergo differential processing through combinatorial splice site selection [1, 2]. This sophisticated processing generates multiple mature mRNA variants (isoforms) through the selective inclusion or exclusion of specific exons or intronic regions [3]. Such transcript diversification dramatically enhances proteomic complexity through the production of structurally and functionally distinct protein products from a single genetic locus. Alternative splicing dysregulation has emerged as a hallmark of human diseases, particularly in malignancies [4]. Growing evidence indicates that cancer cells exploit alternative splicing networks to generate pro-survival isoforms, remodel signaling pathways [5]. Gallbladder cancer (GBC), the most common biliary tract malignancy, is characterized by persistently dismal prognosis and rising global incidence. Current therapeutic approaches remain inadequate, highlighting an urgent need for novel targets and agents [6, 7]. Programmed death-ligand 1 (PD-L1) is a key immune checkpoint molecule expressed on tumor cells that binds to PD-1 on T cells, thereby inhibiting T-cell activation and enabling immune escape [8]. The publication of phase III clinical trial results from KEYNOTE-966 and TOPAZ-1 has substantially reshaped the therapeutic landscape for biliary tract cancer (BTC) through the integration of PD-L1/PD-1 immune checkpoint inhibitors [9, 10]...