DDX39B, a DExD RNA helicase, is known to be involved in various cellular processes such as mRNA export, splicing and translation. Previous studies showed that the overexpression of DDX39B promotes the global translation but inhibits the mRNA export in a dominant negative manner. This presents a conundrum as to how DDX39B overexpression would increase the global translation if it inhibits the nuclear export of mRNAs. We resolve this by showing that DDX39B affects the levels of pre-ribosomal RNA by regulating its stability as well as synthesis. Furthermore, DDX39B promotes proliferation and colony forming potential of cells and its levels are significantly elevated in diverse cancer types. Thus, increase in DDX39B enhances global translation and cell proliferation through upregulation of pre-ribosomal RNA. This highlights a possible mechanism by which dysregulation of DDX39B expression could lead to oncogenesis.

Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we identified Retinal dehydrogenase 1 (ALDH1A1) as a potential interaction partner of PRMT3 and confirmed this interaction using different methods. ALDH1A1 regulates variety of cellular processes by catalyzing the conversion of retinaldehyde to retinoic acid. By molecular docking and site-directed mutagenesis, we identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. Our findings show that in addition to regulating protein functions by introducing methylation modifications, PRMT3 could also regulate global gene expression through protein-protein interactions.

Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.

Protein arginine methyltransferase 5 (PRMT5) symmetrically dimethylates arginine residues in various proteins affecting diverse cellular processes such as transcriptional regulation, splicing, DNA repair, differentiation, and cell cycle. Elevated levels of PRMT5 are observed in several types of cancers and are associated with poor clinical outcomes, making PRMT5 an important diagnostic marker and/or therapeutic target for cancers. Here, using yeast two-hybrid screening, followed by immunoprecipitation and pull-down assays, we identify a previously uncharacterized protein, FAM47E, as an interaction partner of PRMT5. We report that FAM47E regulates steady-state levels of PRMT5 by affecting its stability through inhibition of its proteasomal degradation. Importantly, FAM47E enhances the chromatin association and histone methylation activity of PRMT5. The PRMT5–FAM47E interaction affects the regulation of PRMT5 target genes expression and colony-forming capacity of the cells. Taken together, we identify FAM47E as a protein regulator of PRMT5, which promotes the functions of this versatile enzyme. These findings imply that disruption of PRMT5–FAM47E interaction by small molecules might be an alternative strategy to attenuate the oncogenic function(s) of PRMT5.

Despite significant therapeutic advances, T2DM remains a global public health challenge that leads to multiple complications, including cardiovascular, renal, hepatic, and neurodegenerative disorders. Mitochondrial dysfunction and impaired mitophagy remain fundamental, yet incompletely understood, mechanisms driving pancreatic β-cell failure, chronic inflammation, insulin resistance and diabetic complications. Emerging evidence indicates that noncoding RNAs (including microRNAs, long noncoding RNAs, and circular RNAs) are critical regulators of mitophagy and mitochondrial quality control mechanisms across metabolically active tissues. This review comprehensively examines the interplay between mitochondrial dysfunction, mitophagy impairment, and T2DM pathophysiology. It provides an overview of recent mechanistic insights into mitophagy–noncoding RNA interactions in T2DM, emphasizing tissue-specific effects, and highlights the translational potential of mitophagy-associated proteins and regulatory ncRNAs as diagnostic biomarkers and therapeutic targets. By bridging fundamental molecular biology with translational and clinical perspectives, further it provides a comprehensive framework to guide future research, accelerate biomarker discovery, and support the development of personalized interventions aimed at reducing the growing worldwide burden of T2DM and its complications.