Alternative polyadenylation links RNA processing to iron metabolism in human erythropoiesis - PubMed
2 days ago
- #Erythropoiesis
- #Iron metabolism
- #Alternative polyadenylation
- Alternative polyadenylation (APA) plays a crucial role in erythropoiesis by linking RNA processing to iron metabolism.
- Seven distinct APA dynamic patterns were identified during erythropoiesis, with genes showing stage-specific APA changes enriched in erythroid lineage differentiation, heme synthesis, and iron metabolism.
- CPSF6, a critical APA regulator, facilitates erythropoiesis, and its depletion impairs heme synthesis and causes intracellular iron deficiency.
- CPSF6 depletion shortens the 3'UTR length of iron metabolism regulators (FAM210B, IREB2, TFRC), reducing their expression.
- CPSF6 and APA-regulated iron metabolism-related genes are aberrantly upregulated in polycythemia vera (PV) patients, correlating with erythroid hyperproliferation.
- The findings suggest a CPSF6-APA-iron homeostasis axis as a key co-/post-transcriptional regulatory mechanism in erythropoiesis and implicate its dysregulation in PV pathogenesis.