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. 2020 Sep 2;10(24):11049–11062. doi: 10.7150/thno.49168

Table 2.

Biological characteristics of SE-ncRNAs

SE-ncRNAs Definition Biogenesis mechanism Functions Ref.
miRNAs MicroRNAs are small endogenous RNAs which are 19 to 25 nucleotides in size that regulate post-transcriptional gene expression. MicroRNAs are transcribed from endogenous gene sequences to form hairpin pri-miRNAs, which are processed by Drosha/DGCR8 and further cleaved by Dicer to form mature miRNAs. SEs enhance the transcription and promote the maturity of pri-miRNAs by recruiting Drosha/DGCR8. 1) MicroRNAs can bind to the 3'-UTR region of the target mRNA and inhibit the target genes' expression at the translation level;
2) miRNAs can bind to the coding region or ORF region of the target mRNA to affect its stability;
3) miRNAs enter the nucleus and regulate the target genes' expression at the transcriptional level.
8, 30
lncRNAs Long non-coding RNAs have a transcribing length of 200-100000 nt, lack a completely functional open reading frame (ORF), rarely encode a functional short peptide, and are located in nucleus or cytoplasm. Five main mechanisms of lncRNA biogenesis:1) Transformation from a protein-coding gene that acquires frame disruptions;
2) Chromosome rearrangement;
3, 4) Neighboring repeats originating from two tandem duplications;
5) Insertion by a transposable element to become a functional ncRNA.
The molecular functions of lncRNAs at the epigenetic, transcriptional, and post-transcriptional levels are subdivided as follows: 1) recruiting and interacting with proteins; 2) acting as a co-regulator or a co-repressor; 3) acting as a decoy; 4) acting as host genes for miRNA; 5) interacting with miRNA. 31, 32
circRNAs Circular RNAs are composed of >200 nucleotides and have a covalent closed loop structure without a 5' cap and/or a 3' poly (A), which can encode a small amount of polypeptide. They are mainly produced by cyclization of exons and/or introns. They can be divided into different types, according to the method of cyclization:
1) Formation by spliceosome-dependent cable tail patching;
2) Cis-acting elements promoting formation;
3) RNA binding proteins regulating circRNA formation.
1) Circular RNAs can act as miRNA sponges. They can indirectly regulate miRNA downstream target genes' expression by preventing miRNAs from binding to the 3' untranslated regions of the mRNA;
2) They combine with RNA binding proteins (RBP), playing an important role in changing RNA splicing modes and mRNA stability;
3) They can also act as “miRNA reservoirs,” which can release large amounts of miRNAs under certain circumstances to inhibit the expression of target genes.
33-35
eRNAs Enhancer RNA was identified as a self-transcription of the enhancer itself, with a sequence length of 0.5-5 kb. Enhancer RNAs are transcribed from putative enhancer regions marked by histone modifications, such as H3K4m1/2 and H3K27Ac, and enriched with many transcription factors, such as LDTFs, P300, CBP, BRD4, and MED1. Recently eRNAs transcribed from super enhancers were named super-enhancer RNAs (seRNAs). 1) They synchronously combine with enhancers and promoters and enhance their interaction to stabilize the chromatin loop;
2) eRNAs initiate the transcription of targets by binding to promoters directly or indirectly via recruitment of RNA polymerase II;
3) eRNAs promote target transcription by enhancing the binding of RNA polymerase II;
4) eRNAs act as a decoy for the negative elongation factor (NELF) complex and prompt the elongation of the paused RNA polymerase II.
36, 37