ALYREF (Aly/REF Export Factor)

m5C modifications are globally altered in HBV-negative HCC and may contribute to post-transcriptional regulation and aberrant expression. These findings highlight the potential of m5C as both a prognostic biomarker and a therapeutic target in HBV-negative HCC.

Meanwhile, reader proteins YBX1 and ALYREF maintain the stability of m5C-modified RNAs and activate proliferative and pro-invasive signaling pathways, including PI3K/AKT, mTOR, and Hippo/Wnt. In addition, m5C plays a pivotal role in shaping the tumor immune microenvironment and modulating immune checkpoint activity, thereby influencing the responsiveness and resistance of lung cancer to radiotherapy, chemotherapy, targeted therapy, and immunotherapy.

Our study established lactylation modifications as a crucial regulator of the TME and glioma progression. Through integrative multi-omics analysis and robust machine learning techniques, we determined that RAN was a novel lactylation-associated gene. RAN is a potent, independent prognostic biomarker that promotes glioma malignancy via the PI3K/AKT pathway. Our results demonstrate RAN as a prospective therapeutic target and establish a novel framework for individualized therapy for glioma.

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.