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Review
, 5 (1)

Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease

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Review

Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease

Juliane C R Fernandes et al. Noncoding RNA.

Abstract

The identification of RNAs that are not translated into proteins was an important breakthrough, defining the diversity of molecules involved in eukaryotic regulation of gene expression. These non-coding RNAs can be divided into two main classes according to their length: short non-coding RNAs, such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). The lncRNAs in association with other molecules can coordinate several physiological processes and their dysfunction may impact in several pathologies, including cancer and infectious diseases. They can control the flux of genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability, and post-translational modifications. Long non-coding RNAs present interaction domains for DNA, mRNAs, miRNAs, and proteins, depending on both sequence and secondary structure. The advent of new generation sequencing has provided evidences of putative lncRNAs existence; however, the analysis of transcriptomes for their functional characterization remains a challenge. Here, we review some important aspects of lncRNA biology, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.

Keywords: biomarkers; chromosome; gene expression; infectious diseases; long non-coding RNA; microRNA; nuclear architecture; physiology.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the genomic loci of different long non-coding RNA (lncRNA) and circular RNA (circRNA) biogenesis. (A) lncRNA classification depends on the genomic position: (i) intergenic RNAs (lincRNAs) are located between two protein coding-genes, (ii) intronic lncRNAs are positioned within an intronic region of a protein coding-gene, (iii) antisense lncRNAs (aslncRNAs) are transcribed from complementary strands, (iv) bidirectional lncRNAs originate from bidirectional transcription of protein-coding genes, and (v) enhancer RNAs (eRNAs) originate from enhancer regions and mediate transcription factor positioning into protein coding-genes promoters. (B) circRNAs are lncRNAs that undergo back splicing and can originate from transcripts containing only intronic, one or more exonic, or both intronic and exonic fragments (elciRNAs).
Figure 2
Figure 2
LncRNA participation in gene expression regulation. Many types of lncRNA controls can occur to regulate gene expression, such as: (1) chromatin and chromosome condensation through histone modifications, (2) transcription factors (TF) direct recruitment, (3) binding to RNA polymerase (pol) II, (4) alternative splicing, (5) mRNA stability, (6) miRNA availability, (7) polysomes recruitment, and (8) modulation of gene expression in neighbor cells through packaging into extracellular vesicles.
Figure 3
Figure 3
Interaction between microRNAs (miRNAs) and lncRNAs. (A) lncRNAs can act as miRNA sponges in both linear or circular forms, thus reducing interaction between miRNA-target mRNA; (B) lncRNA can harbor miRNA precursors, producing mature miRNAs after Dicer and/or Drosha cleavage; (C) miRNA can target lncRNA for degradation, similar to 3’ untranslated region binding to mRNAs; and (D) lncRNA–miRNA competition for the mRNA binding site. circRNA—circular lncRNA; AGO—argonaute proteins; miRISC—miRNA-induced silencing complex; Dicer—endoribonuclease; Drosha—endoribonuclease.
Figure 4
Figure 4
Patho-physiological implications of lncRNAs expression in a time- and infection-dependent manner. (A) Expression of HOTAIR complexed with PRC2 and LSD1 leads to trimethylation of the histone 3 at the lysine 27 and demethylation of the lysine 4, controlling gene expression during embryonic development, but leading to breast cancer metastasis when expressed in adult breast tissue; (B) disruption of the NRON lncRNA expression in T CD4+ lymphocyte by the HIV Nef protein leads to NFAT translocation to the nucleus and LTR transcription. Abbreviations: HOTAIR—Hox transcript antisense intergenic RNA; PRC2—polycomb repressive complex; LSD1—lysine-specific histone demethylase 1; Me—methyl groups; H—histone; K—lysine; NEF—negative regulatory factor, NRON—non-coding repressor of NFAT; NFAT—nuclear factor of activated T-cells; HIV—human immunodeficiency virus; LTR—long terminal repeat; T CD4—CD4 T lymphocytes.

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References

    1. Long Y., Wang X., Youmans D.T., Cech T.R. How do lncRNAs regulate transcription? Sci. Adv. 2017;3:eaao2110. doi: 10.1126/sciadv.aao2110. - DOI - PMC - PubMed
    1. Blin N., Stephenson E.C., Stafford D.W. Isolation and some properties of a mammalian ribosomal DNA. Chromosoma. 1976;58:41–50. doi: 10.1007/BF00293439. - DOI - PubMed
    1. Stephenson M.L., Zamecnik P.C. Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc. Natl. Acad. Sci. USA. 1978;75:285–288. doi: 10.1073/pnas.75.1.285. - DOI - PMC - PubMed
    1. Küpper H., Sekiya T., Rosenberg M., Egan J., Landy A. A Rho-dependent termination site in the gene coding for tyrosine tRNA su3 of Escherichia Coli. Nature. 1978;272:423–428. doi: 10.1038/272423a0. - DOI - PMC - PubMed
    1. Derrien T., Johnson R., Bussotti G., Tanzer A., Djebali S., Tilgner H., Guernec G., Martin D., Merkel A., Knowles D.G., et al. The gencode v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res. 2012;22:1775–1789. doi: 10.1101/gr.132159.111. - DOI - PMC - PubMed
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