遗传学报2024，Vol.51Issue(6) ：594-607.DOI:10.1016/j.jgg.2024.02.003

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
遗传学报2024，Vol.51Issue(6) ：594-607.DOI:10.1016/j.jgg.2024.02.003
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The non-canonical poly(A)polymerase FAM46C promotes erythropoiesis

Ke Yang 1Tianqi Zhu 2Jiaying Yin 3Qiaoli Zhang 2Jing Li 3Hong Fan 3Gaijing Han 3Weiyin Xu 2Nan Liu 2Xiang Lv4
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作者信息

  • 1. Bone Marrow Transplantation Center,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310003,China;Liangzhu Laboratory,Zhejiang University,Hangzhou,Zhejiang 311121,China;Institute of Hematology,Zhejiang University,Hangzhou,Zhejiang 311121,China;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,B
  • 2. Bone Marrow Transplantation Center,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310003,China;Liangzhu Laboratory,Zhejiang University,Hangzhou,Zhejiang 311121,China;Institute of Hematology,Zhejiang University,Hangzhou,Zhejiang 311121,China
  • 3. 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
  • 4. 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;Medical Epigenetics Research Center,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100005,China
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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 mito-chondria 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.

Key words

FAM46C/TENT5C/Poly(A)polymerase/Erythroblasts/Post-transcriptional regulation/Erythroid-specific enhancer

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基金项目

Starting Fund from Zhejiang University to N.L.and grants to X.L.from National Natural Science Foundation of China(82170120)

Starting Fund from Zhejiang University to N.L.and grants to X.L.from National Natural Science Foundation of China(81670108)

CAMS Initiative for Innovative Medicine(2017-I2M-B&R-04)

Medical Epigenetics Research Center,CAMS(2018PT31015)

State Key Laboratory of Medical Molecular Biology(2060204)

Haihe Laboratory of Cell Ecosystem Innovation Fund(22HHXBSS00008)

出版年

2024
遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
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