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. 2017 Oct-Dec;9(4):13-25.

Non-Coding RNAs As Transcriptional Regulators In Eukaryotes

O Y Burenina  1   2 , T S Oretskaya  2   3 , E A Kubareva  3
Affiliations

Non-Coding RNAs As Transcriptional Regulators In Eukaryotes

O Y Burenina et al. Acta Naturae. 2017 Oct-Dec.

Abstract

Non-coding RNAs up to 1,000 nucleotides in length are widespread in eukaryotes and fulfil various regulatory functions, in particular during chromatin remodeling and cell proliferation. These RNAs are not translated into proteins: thus, they are non-coding RNAs (ncRNAs). The present review describes the eukaryotic ncRNAs involved in transcription regulation, first and foremost, targeting RNA polymerase II (RNAP II) and/or its major proteinaceous transcription factors. The current state of knowledge concerning the regulatory functions of SRA and TAR RNA, 7SK and U1 snRNA, GAS5 and DHFR RNA is summarized herein. Special attention is given to murine B1 and B2 RNAs and human Alu RNA, due to their ability to bind the active site of RNAP II. Discovery of bacterial analogs of the eukaryotic small ncRNAs involved in transcription regulation, such as 6S RNAs, suggests that they possess a common evolutionary origin.

Keywords: RNA polymerase; noncoding RNAs; transcription regulation.

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Figures

Fig. 1
Fig. 1
The best known ncRNAs acting as transcriptional activators (green) or inhibitors (purple) via interactions with RNAP II and/or its general transcription factors (TF) or with other regulatory proteins, in particular nuclear receptors (NR).
Fig. 2
Fig. 2
Scheme of the functioning of murine B1 RNA (A) and human Alu RNA (B). Secondary structures of ncRNAs are schematically shown on the left. Alu RNA structural elements responsible for transcription inhibition are in light-blue frames, the functional domain (Alu-RA) is colored in blue, the A-rich linker is shown by a dash line. A schematic view of interactions between RNAP II and B1, scAlu, or Alu RNA is shown on the right. Transcription is indicated by a black arrow. B1 and scAlu RNA are displaced by TFIIF from their complexes with RNAP II, thus, they are unable to inhibit transcription, in contrast to Alu RNA.
Fig. 3
Fig. 3
Scheme of the functioning of murine B2 RNA. (A) Simplified view of the B2 RNA secondary structure. Disordered parts are shown by a dash line; functional part – by a blue line; inhibitory domain is in a light-blue frame. (B) B2 RNA prevents initiation of transcription by “switching off” TFIIH kinase activity. The Ser2 and Ser5 amino acid residues are marked as “S2” and “S5,” phosphorylation – as “P” in a circle. (C) The sequence of the 3’-end fragment (145–178 nt) of B2 RNA extended by additional 18 nt [34]. (D) Elongation of B2 RNA 3’-end (eB2 RNA) leads to the formation of a new hairpin (pink), which causes conformational changes in RNAP II (shown by a grey arrow) and dissociation of B2 RNA. Transcription on a DNA template is indicated by a black arrow, transcription on a B2 RNA template – by a pink arrow.
Fig. 4
Fig. 4
Scheme of the functioning of U1 snRNA (A) and DHFR ncRNA (B). The simplified secondary structure of U1 snRNA is adapted from [37]. There is no structural data for DHFR ncRNA. U1 snRNA activates transcription (shown by green arrow) by stimulating the TFIIH-dependent phosphorylation of RNAP II Rpb1 CTD. DHFR ncRNA inhibits transcription by displacing the TFIIB transcription factor from PIC.
Fig. 5
Fig. 5
Transcription regulation involving human 7SK snRNA and HIV TAR RNA. (A) General steps of transcription conducted by RNAP II [46]. For transcription initiation, TFIIH phosphorylates Ser5 residues in RNAP Rpb1 CTD. The enzyme stops after the synthesis of a small transcript and the negative elongation factors NELF and DSIF bind to RNAP, resulting in transcription pause. After 5’-capping of a nascent RNA strand transcription restarts: DNA-binding proteins attract the P-TEFb factor, which further phosphorylates RNAP Rpb1 CTD and the factors NELF and DSIF. The latter turns into a transcription activator (DSIF*, shown in green), and modified NELF dissociates from the complex, that enables RNAP to proceed to the transcription elongation step. (B) Assembly of alternative protein complexes on 7SK snRNA. Binding of RHA and hnRNP to the 7SK snRNP core prevents the inhibition of P-TEFb. The HIV protein Tat can displace P-TEFb from 7SK snRNP and attract it to RNAP, arrested near the transcription start site. TAR RNA interacts with Tat and CycT and activates the kinase activity of P-TEFb, resulting in hyperphosphorylation of RNAP Rpb1 CTD and NELF/DSIF, followed by elongation of a viral transcript.
Fig. 6
Fig. 6
Schematic representation of the secondary structure of human SRA RNA (A) and its currently known protein partners (B) according to Liu et al. [61]. SRA RNA domains are colored: D1 – green, D2 – black, D3 – blue, D4 – grey. The U207 residue subjected to pseudouridilation is marked by an asterisk. Panel A shows the main structural elements of SRA RNA that bind several proteins, shown in color frames. Panel B shows a schematic representation of the proteins which directly bind to SRA RNA (they are labeled in corresponding colors). Nuclear receptors (AR – androgen, PR – progesterone, ERα – estrogen α) are colored in blue. All other proteins known to interact with SRA RNA are denoted in grey (without animation).
Fig. 7
Fig. 7
Inhibition of the transcription of glucocorticoid-dependent genes by GAS5 RNA. (A) Predicted GAS5 RNA secondary structure (top) and nucleotide sequence of the functional element (hairpin), containing the GRE-1 and GRE-2 regions that mimic DNA promoter (bottom). The key residues G540 and C554 are shown in pink. The GAS5 RNA domain responsible for the interaction with the HCV NS3 protein is colored in green. Central part of the molecule which is a target for miR binding is shown as a grey dash line (secondary structure is unknown). Both domains apparently do not participate in transcription regulation. (B) GAS5 RNA inhibits transcription by binding nuclear receptors and preventing their interaction with GRE-containing promoters.
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References

    1. Yang Z., Li X., Yang Y., He Z., Qu X., Zhang Y.. Cell Death Dis. 2016;7(9):e2389. - PMC - PubMed
    1. Francia S., Front Genet. 2015;13(6):320. - PubMed
    1. Kaikkonen M.U., Lam M.T.Y., Glass C.K.. Cardiovasc. Res. 2011;90(3):430–440. - PMC - PubMed
    1. Castelnuovo M., Stutz F.. Curr. Opin. Cell Biol. 2015;34:16–22. - PubMed
    1. Esteller M.. Nat. Rev. Genet. 2011;12(12):861–874. - PubMed

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