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

Ke Yang; Tianqi Zhu; Jiaying Yin; Qiaoli Zhang; Jing Li; Hong Fan; Gaijing Han; Weiyin Xu; Nan Liu; Xiang Lv

doi:10.1016/j.jgg.2024.02.003

Volume 51 Issue 6

Jun. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(6): 594-607

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

doi: 10.1016/j.jgg.2024.02.003

Ke Yang^a,b,c,d,
Tianqi Zhu^a,b,c,
Jiaying Yin^d,
Qiaoli Zhang^a,b,c,
Jing Li^d,
Hong Fan^d,
Gaijing Han^d,
Weiyin Xu^a,b,c,
Nan Liu^a,b,c,
Xiang Lv^d,e

a. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China;
b. Liangzhu Laboratory, Zhejiang University, Hangzhou, Zhejiang 311121, China;
c. Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 311121, China;
d. The State Key Laboratory for Complex, Severe, and Rare Diseases, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China;
e. Medical Epigenetics Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China

Funds:

R-04), Medical Epigenetics Research Center, CAMS (2018PT31015), the State Key Laboratory of Medical Molecular Biology (2060204), and Haihe Laboratory of Cell Ecosystem Innovation Fund (22HHXBSS00008).
We would like to thank Junxin Lin and Wanlu Liu (Zhejiang University – University of Edinburgh Institute) for providing ADARcd vector. We would thank Di Chen lab (Zhejiang University – University of Edinburgh Institute) for providing APOBEC1 vector and suggestions about experiment design. We thank the technical support by the core facilities and computing platform of Zhejiang University Medical Center and Liangzhu Laboratory.

This work is funded by the Starting Fund from Zhejiang University to N.L. and grants to X.L. from National Natural Science Foundation of China (82170120 and 81670108), CAMS Initiative for Innovative Medicine (2017-I2M-B&

Received Date: 2023-10-23
Accepted Date: 2024-02-19
Rev Recd Date: 2024-02-19

Available Online: 2025-06-06

Publish Date: 2024-02-24

Abstract

Abstract

The post-transcriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process has detrimental effects on the normal development and gives rise to various diseases. Searching for novel post-transcriptional regulators and exploring their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait genome-wide association studies (GWAS) and transcriptomes of erythropoiesis, we identify 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 identify 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 unique role of FAM46C in positively regulating lysosome and mitochondria components, thereby promoting erythropoiesis.
- FAM46C,
- TENT5C,
- Poly(A) polymerase,
- Erythroblasts,
- Post-transcriptional regulation,
- Erythroid-specific enhancer

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References

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