Abstract
MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that participate in a majority of biological processes via regulating target gene expression. The post-transcriptional repression through miRNA seed region binding to 3′ UTR of target mRNA is considered as the canonical mode of miRNA-mediated gene regulation. However, emerging evidence suggests that other regulatory modes exist beyond the canonical mechanism. In particular, the function of intranuclear miRNA in gene transcriptional regulation is gradually revealed, with evidence showing their contribution to gene silencing or activating. Therefore, miRNA-mediated regulation of gene transcription not only expands our understanding of the molecular mechanism underlying miRNA regulatory function, but also provides new evidence to explain its ability in the sophisticated regulation of many bioprocesses. In this review, mechanisms of miRNA-mediated gene transcriptional and post-transcriptional regulation are summarized, and the synergistic effects among these actions which form a regulatory network of a miRNA on its target are particularly elaborated. With these discussions, we aim to emphasize the importance of miRNA regulatory network on target gene regulation and further highlight the potential application of the network mode in the achievement of a more effective and stable modulation of the target gene expression.
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Abbreviations
- AGO:
-
Argonaute proteins
- ASO:
-
Antisense oligonucleotides
- CYP2E1:
-
Cytochrome P450 (CYP) 2E1
- DGCR8:
-
DiGeorge syndrome chromosomal [or critical] region 8
- DOX:
-
Doxorubicin
- HCV:
-
Hepatitis C virus
- IPO8:
-
Importin 8
- miRISC:
-
MicroRNA-induced silencing complex
- miRNA:
-
MicroRNA
- nt:
-
Nucleotides
- NPC:
-
Nuclear pore complex
- snoRNA:
-
Small nucleolar RNA
- SMARCE1:
-
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1
- PTGS:
-
Post-transcriptional gene silencing
- pre-miRNAs:
-
Precursor miRNAs
- P-body:
-
Processing body
- Pol II:
-
Polymerase II
- RNAi:
-
RNA silencing
- TRBP:
-
Transactivation-responsive RNA-binding protein
- TGS:
-
Transcriptional gene silencing
- TGA:
-
Transcriptional gene activating
- trnc6a:
-
Trinucleotide repeat-containing gene 6A
- UTR:
-
Untranslated region
- XPO5:
-
Exportin-5
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Pu, M., Chen, J., Tao, Z. et al. Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression. Cell. Mol. Life Sci. 76, 441–451 (2019). https://doi.org/10.1007/s00018-018-2940-7
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DOI: https://doi.org/10.1007/s00018-018-2940-7