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

作　　者：Ke Yang Tiangi Zhu Jiaying Yin Qiaoli Zhangg Jing Li Hong Fan Gajing Han Weiyin Xu Nan Liu Xiang Lv 

机构地区：[1]Bone Marrow Transplantation Center,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310003,China [2]Liangzhu Laboratory,Zhejang University,Hangzhou,Zhejang 311121,China [3]Institute of Hematology,Zhejiang University,Hangzhou,Zhejiang 311121,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 [5]Medical Epigenetics Research Center,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China

出　　处：《Journal of Genetics and Genomics》2024年第6期594-607,共14页遗传学报（英文版）

基　　金：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(2017-12M-B&R-04);Medical Epigenetics Research Cen-ter,CAMS(2018PT31015);the State Key Laboratory of Medical Molecular Biology(2060204);Haihe L aboratory of Cell Ecosystem Innovation Fund(22HHXBSS00008).

摘　　要：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 erythroidspecific 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.

关 键 词：FAM46C TENT5C Poly(A)polymerase ERYTHROBLASTS Post-transcriptional regulation Erythroid-specific enhancer 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]