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

  • Wen-Ting Guo
  • Yangming WangEmail author
Review
  • 114 Downloads

Abstract

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.

Keywords

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

Abbreviations

APA

Alternative polyadenylation

AGO

Argonaute

cKO

Conditional knockout

cNCCs

Cardiac neural crest cells

COX-2

Cyclooxygenase 2

cTECs

Cortical thymic epithelial cells

DGCR

DiGeorge syndrome chromosomal (or critical) region

DISME

DGCR8-independent stable miRNA expression strategy

EMT

Epithelial–mesenchymal transition

EpiLC

Epiblast-like cells

EpiSCs

Epiblast stem cells

ESC

Embryonic stem cell

ESCC

ESC-specific cell cycle regulating

GPCs

Glia progenitor cells

iKO

Inducible knockout

iPSCs

Induced pluripotent stem cells

LINE-1

Long interspersed element 1

lncRNA

Long noncoding RNA

MC

Microprocessor complex

miRNA

microRNA

mTECs

Medullary thymic epithelial cells

NK

Natural killer

NSCs

Neural stem cells

PACT

Protein activator of PKR

PTA

Persistent truncus arteriosus

RISC

RNA-induced silencing complex

RPE

Retinal pigmented epithelium

rRNA

Ribosomal RNA

SCs

Schwann cells

Shh

Sonic hedgehog

shRNA

Short hairpin RNA

snoRNA

Small nucleolar RNA

TDP43

TAR DNA-binding protein 43

TECs

Thymic epithelial cells

TRBP

HIV trans-activating response RNA-binding protein

Th cells

Helper T cells

tRNA

Transfer RNA

VSD

Ventricular septal defect

Notes

Acknowledgements

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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