ALYREF (Aly/REF Export Factor)

In this study, we integrated RNA-Seq and single-cell transcriptomic data from cisplatin-resistant ovarian cancer cell lines and patient samples, identifying the m5C reader protein ALYREF as a key regulator of platinum resistance...Together, our findings demonstrate that the NSUN2/ALYREF/LGR4 axis mediates platinum resistance through m5C-dependent stabilization of LGR4 and downstream Wnt signaling activation. Thus, targeting ALYREF may represent a promising strategy to overcome platinum resistance in ovarian cancer.

Finally, ALYREF and PARP10 expression correlate with poor prognosis in ovarian cancer patients. Together, these findings suggest that ALYREF phase separation facilitates the malignant progression of ovarian cancer by promoting PARP10 expression and thereby enhancing PARP10-dependent proliferative pathways in a m5C-dependent manner.

Its overexpression signifies aggressive tumor biology and metastatic risk yet also predicts a favorable response to immunotherapy. ALYREF holds promise for refining patient stratification and personalizing BCa treatment.

In summary, our results suggest that YBX1/ALYREF correlates with HIF1α and accelerates malignant progression of GC through affecting cell migration. The function mode of YBX1 and ALYREF provides a new insight for the diagnosis of GC and lays a foundation for the development of epigenetic antitumor drugs.

While many questions remain, these advances have deepened our understanding of nuclear mRNA metabolism and offer new opportunities to investigate how disruptions in mRNA biogenesis and export factors, and their associated processes, contribute to disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Export and Localization > Nuclear Export/Import.

ALYREF stabilized CREPT mRNA through interacting with m5C-labelled CREPT mRNA to elevate CREPT expression, thus activating Wnt/β-catenin pathway and facilitating NPC progression.

Conversely, the m6A writer METTL14 was downregulated. Our findings highlight key mRMPs as potential biomarkers and therapeutic targets, underscoring the role of RNA modifications in breast cancer progression.

Rescue experiments indicated that BUB1 overexpression partially reversed the inhibitory effect of KIF20A knockdown on hypoxia-mediated ferroptosis resistance in CC cells. In conclusion, hypoxia triggers ALYREF-mediated m5C methylation of KIF20A to activate the KIF20A/BUB1 axis, thereby inducing ferroptosis resistance in CC cells.

Consequently, disruption of ALYREF LLPS leads to dissociation of the NARC1 complex, resulting in DNA damage and apoptosis in CMs. Collectively, these findings reveal a previously unrecognized mechanism by which DIC via interference with ALYREF condensates, offering new insight into the molecular basis of DIC.

This study identified a novel NSUN2/ALYREF/m5C-PHGDH axis might be promising therapeutic targets for CRC.

Moreover, we validate the efficacy of cholesterol biosynthesis inhibitor simvastatin in ESCC with high TTPAL expression. Overall, our results uncover a novel function of TTPAL in regulating SREBP2 expression, revealed a previously unknown TTPAL/NSUN2/SREBP2 pathway that promotes cholesterol biosynthesis in ESCC cells, and identified sensitively to cholesterol biosynthesis inhibitor simvastatin.

Two subtypes of m5C regulators in ESCA patients were explored. Our findings may improve the understanding of m5C regulators in the biology of ESCA.