Bladder cancer (BLCA) is a common and heterogeneous malignancy in which disease progression is driven not only by tumor-intrinsic alterations but also by dynamic interactions within the tumor microenvironment (TME). Increasing evidence positions the extracellular matrix (ECM) as a critical regulator of these processes. Matricellular proteins (MCPs), a group of nonstructural ECM-associated molecules, have emerged as key modulators of tumor–stroma communication. In BLCA, MCPs have been reported to display divergent, and in some cases opposing, associations or functions, with the same protein participating in both tumor promotion and suppression. Here, we review current evidence on the function of MCPs in BLCA and synthesize their bidirectional roles in carcinogenesis. MCPs contribute to tumor progression by promoting invasion, epithelial–mesenchymal transition (EMT), angiogenesis, and metastatic niche formation. At the same time, MCPs can restrain tumor growth by inhibiting angiogenesis, stabilizing ECM organization, inducing cell cycle arrest, and maintaining epithelial integrity. A key concept emerging from this body of evidence is the context-dependent functional plasticity of MCPs. We propose that MCP-associated phenotypes in BLCA may be influenced by contextual factors, including isoform diversity arising from alternative splicing and post-translational modifications, spatial compartmentalization within tumor and stromal niches, tumor microenvironmental composition, and molecular subtype. However, the level of supporting evidence differs substantially among MCPs, and direct BLCA-specific mechanistic evidence remains limited for many proposed relationships. These factors, therefore, provide a framework for interpreting divergent findings rather than representing universally established determinants of MCP function. Recognizing MCPs as context-sensitive regulators rather than fixed tumor-promoting or tumor-suppressing entities provides a unifying framework for understanding their roles in BLCA. This could be an important step for therapeutic targeting, encouraging effective strategies to consider and incorporate the molecular and microenvironmental context in which MCPs operate.

Gene duplication underlies evolutionary innovation, yet many paralogues remain highly similar, raising questions about their functional divergence and physiological relevance. The spliceosomal Sm core protein SNRPB and its mammalian-specific paralogue SNRPN share over 90% sequence identity, but their distinct expression patterns - SNRPB being ubiquitous and SNRPN confined to the brain - suggest specialized functions. Why mammals have two different spliceosomes has remained obscure. Here, we generated isogenic human cell lines expressing ectopically either SNRPB or SNRPN exclusively and found that SNRPN stabilizes transcripts involved in energy metabolism and mitochondrial function, leading to increased mitochondrial abundance and oxygen consumption. Despite similar spliceosomal interactomes, SNRPN more strongly associates with the PRMT5 methylosome complex and exhibits dynamic arginine methylation in its C-terminal region that is sensitive to translation inhibition and amino acid availability. The SNRPN-dependent transcriptome responds to translation inhibition by stabilizing long, intron-rich genes involved in amino acid and energy metabolism. Our findings reveal a nutrient-sensitive, methylation-dependent mechanism that differentiates the two paralogues. This suggests that SNRPN functions as a metabolic-specialized spliceosomal subunit thereby providing tissue-specific adaptation of RNA processing in mammals.

Background: Rising global temperatures are expected to increase the spread of infectious diseases as warming allows disease-carrying mosquitoes such as Anopheles to survive and reproduce in new regions. To interrogate mosquito gene function rapidly and at scale, we here establish baculovirus as a gene delivery tool in Anopheles cells. We then use this system to express and study the dominant male sex-determining factor Yob, whose molecular function is unknown. Methods: We engineered plasmids with mosquito promoters spanning different strengths, driving genes-of-interest and selection markers, and used them to generate baculoviruses. An. gambiae Ag55 cells were infected over a range of virus doses and exposure durations. Infection efficiency, cell viability, and proliferation were characterized by flow cytometry. We profiled host and viral transcriptional responses by RNA-seq; assessed Yob chromatin association and localization by CUT&Tag and microscopy; and mapped protein-level changes and interactors by proteomics and immunoprecipitation. Results: We found that baculovirus infection blocks cell cycle progression and induces pronounced transcriptome changes, while Yob expression adds an additional male-biased signature. Yob localized to the nucleus but did not directly associate with chromatin by CUT&Tag, suggesting that it does not act as a transcription factor. Yob expression increased the abundance of nuclear RNA-metabolism factors, including DDX5-like helicases and CCR4-NOT-complex subunits, and Yob-HA co-immunoprecipitated with RNA-metabolism proteins. Conclusions: Together, these results demonstrate that the baculovirus system provides a versatile platform for studying mosquito gene biology in vitro. Our results imply that Yob’s mode of action is not classical DNA binding; rather, Yob is a small nuclear factor that modulates RNA-metabolism machinery, inducing a male transcriptional state. Graphical