中国医学科学院Xiang Lv等研究人员合作发现，非经典多聚（A）聚合酶FAM46C促进红细胞生成。该研究于2024年2月24日在线发表于《遗传学报》。

通过对红细胞性状GWAS和红细胞生成转录组的多模态分析，研究人员发现非经典RNA多（A）聚合酶FAM46C是红细胞正常发育的必要因子。FAM46C在红细胞系的后期高度表达，其发育上调受红细胞特异性增强子的控制。研究人员证明了FAM46C能稳定mRNA，并以聚合酶活性依赖的方式调控红细胞的分化。

此外，研究人员还发现溶酶体和线粒体成分的转录本是FAM46C高度可信的体内靶标，这与成熟红细胞需要大量清除细胞器和维持细胞氧化还原平衡的需求相吻合。总之，这项研究揭示了FAM46C在正向调节溶酶体和线粒体成分，从而促进红细胞生成方面的新作用。

据悉，mRNA的转录后调控是基因表达的重要组成部分。这一过程的破坏会对正常发育产生不利影响，并引发各种疾病。寻找新型转录后调控因子并探索其作用对于了解发育和疾病至关重要。

附：英文原文

Title: The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis

Author: anonymous

Issue&Volume: 2024/02/24

Abstract: Posttranscriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process can have detrimental effects on normal development and give rise to various diseases. The search for novel posttranscriptional regulators and the exploration of their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait GWASs and transcriptomes of erythropoiesis, we identified FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in the late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent manner. Furthermore, we identified transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a novel role of FAM46C in positively regulating lysosome and mitochondria components, thereby promoting erythropoiesis.

DOI: 10.1016/j.jgg.2024.02.003

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724000328