Cellular and Molecular Life Sciences

, Volume 76, Issue 9, pp 1697–1711 | Cite as

Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo

  • Wen-Ting Guo
  • Yangming WangEmail author


Biologic function of the majority of microRNAs (miRNAs) is still unknown. Uncovering the function of miRNAs is hurdled by redundancy among different miRNAs. The deletion of Dgcr8 leads to the deficiency in producing all canonical miRNAs, therefore, overcoming the redundancy issue. Dgcr8 knockout strategy has been instrumental in understanding the function of miRNAs in a variety of cells in vitro and in vivo. In this review, we will first give a brief introduction about miRNAs, miRNA biogenesis pathway and the role of Dgcr8 in miRNA biogenesis. We will then summarize studies performed with Dgcr8 knockout cell models with a focus on embryonic stem cells. After that, we will summarize results from various in vivo Dgcr8 knockout models. Given significant phenotypic differences in various tissues between Dgcr8 and Dicer knockout, we will also briefly review current progresses on understanding miRNA-independent functions of miRNA biogenesis factors. Finally, we will discuss the potential use of a new strategy to stably express miRNAs in Dgcr8 knockout cells. In future, Dgcr8 knockout approaches coupled with innovations in miRNA rescue strategy may provide further insights into miRNA functions in vitro and in vivo.


Drosha Cell cycle Glycolysis Alternative splicing Glial progenitor cells Reproductive system Neural system Immune system 



Alternative polyadenylation




Conditional knockout


Cardiac neural crest cells


Cyclooxygenase 2


Cortical thymic epithelial cells


DiGeorge syndrome chromosomal (or critical) region


DGCR8-independent stable miRNA expression strategy


Epithelial–mesenchymal transition


Epiblast-like cells


Epiblast stem cells


Embryonic stem cell


ESC-specific cell cycle regulating


Glia progenitor cells


Inducible knockout


Induced pluripotent stem cells


Long interspersed element 1


Long noncoding RNA


Microprocessor complex




Medullary thymic epithelial cells


Natural killer


Neural stem cells


Protein activator of PKR


Persistent truncus arteriosus


RNA-induced silencing complex


Retinal pigmented epithelium


Ribosomal RNA


Schwann cells


Sonic hedgehog


Short hairpin RNA


Small nucleolar RNA


TAR DNA-binding protein 43


Thymic epithelial cells


HIV trans-activating response RNA-binding protein

Th cells

Helper T cells


Transfer RNA


Ventricular septal defect



The research in Wang laboratory is supported by the National Key Research and Development Program of China (2016YFA0100701 and 2018YFA0107601) and the National Natural Science Foundation of China (31471222, 31622033, 31821091 and 91640116). WTG is supported by the Fundamental Research Funds for the Central Universities (3332018008). Due to the breadth of this review, we apologize for the unavoidable exclusion of references to research done by many outstanding investigators working in relevant areas.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Central Laboratory, Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijingPeople’s Republic of China
  2. 2.Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular MedicinePeking UniversityBeijingPeople’s Republic of China

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