Cellular RNAs: Varied Roles

Jian Gu, The University of Texas MD Anderosn Cancer Center, Houston, Texas, USA
Yifan Xu, The University of Texas MD Anderosn Cancer Center, Houston, Texas, USA

Published online: August 2020

DOI: 10.1002/9780470015902.a0029149

Abstract

About 85% of the human genome is transcribed into RNA. RNAs play essential roles in numerous cellular processes. Less than 2% of all transcripts are coding RNAs (messenger RNA). The remaining vast majority of RNAs do not encode protein and are collectively referred as noncoding RNA (ncRNA). Based on their biological functions, ncRNAs can be grouped into two categories: infrastructural and regulatory ncRNAs. Infrastructural ncRNAs mainly include ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs) and telomerase RNAs. The best‐characterised regulatory ncRNAs are microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Other regulatory ncRNAs include small inhibitory RNAs (siRNAs), Piwi‐interacting RNAs (piRNAs) and circular RNAs (circRNA). This article will summarise the structure and function of major RNA categories.

  • Three RNA types are essential for protein synthesis: mRNA carries genetic code; tRNA transfers protein codon; and rRNA makes up the ribosomes in which translation takes place.
  • About 85% of the human genome is transcribed into RNA. Only <2% of RNAs are coding RNAs (mRNAs) and the remaining RNAs are noncoding RNAs (ncRNAs).
  • Noncoding RNAs can be grouped into two categories: infrastructural and regulatory ncRNAs. Infrastructural ncRNAs mainly include rRNAs, tRNAs, snRNAs, and snoRNAs. The major regulatory ncRNAs include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs).
  • SnRNAs are often rich in uridylic acid and a group of U‐snRNAs and associated proteins form spliceosome and are responsible for pre‐mRNA splicing.
  • SnoRNAs can be classified into two large subfamilies: C/D‐box (SNORA) and H/ACA‐box (SNORD). The main functions of snoRNAs are in the processing and maturation of pre‐rRNAs and posttranscriptional modification (methylation and pseudouridylation) of rRNA.
  • Three small ncRNAs, siRNA, miRNA and piRNA, form RNA‐induced silencing complex (RISC) to exert posttranscriptional gene regulation by binding to 3′ UTR of target mRNAs and either inducing mRNA degradation (perfect match) or impeding translation (imperfect match).
  • miRNAs are the major type of small ncRNAs. The biogenesis of miRNAs is a multistep process, from long primary miRNA transcripts (pri‐miRNAs) to pre‐miRNAs of ∼70 nucleotides long and to mature miRNA of ∼22 nucleotides.
  • piRNAs mainly function in the germ line of animals to silence transposons and other repetitive elements and maintain genomic stability.
  • lncRNAs are >200 nucleotides long. There are thousands of lncRNAs and the majority have not been functionally characterised. But many have been shown to posttranscriptionally regulate gene expression through various mechanisms.
  • Unlike the better‐known linear RNA, circRNAs is a type of single‐stranded RNA that are covalently closed with no 5′ end caps or 3′ poly(A) tails. Some circRNAs can serve as miRNA and protein sponges to sequester miRNA/protein and regulate gene expression.

Keywords: translation; transcription; noncoding RNA; lncRNA; microRNA; spliceosome; RNA interference; RNA‐induced silencing complex (RISC)

Figure 1. A comparison of the prokaryotic and eukaryotic ribosomal RNAs. The large subunit (LSU) is shown in blue and the small subunit (SSU) is shown in yellow. (a) In prokaryotes, there are three types of rRNA: 5S and 23S rRNAs in LSU, 16S rRNA in SSU. (b) In eukaryotes, there are four types of rRNA: 5S, 5.8S and 28S rRNAs in LSU, 18S rRNA in SSU.
Figure 2. A simplified view of the spliceosome assembly and rearrangement. U1 snRNPs binds to the 5′ splice site, U2 subsequently binds to the branch site and then U4/U5/U6 triple snRNPs join in. After a dynamic rearrangement, U1 and U4 are destabilised, and the spliceosome is activated for the two steps of cleavage–ligation event.
Figure 3. A simplified view of the miRNA biogenesis and function. Pri‐miRNAs that are transcribed by RNA Polymerase II are processed by Drosha to generate pre‐miRNAs in nucleus. Pre‐miRNAs are exported to cytoplasm by exportin 5 and processed by Dicer to generate mature miRNAs. Mature miRNAs form RISC/Ago complex and target the 3′ UTR of mRNAs to suppress gene expression by mRNA degradation or translation inhibition.
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References

Barrett SP and Salzman J (2016) Circular RNAs: analysis, expression and potential functions. Development 143 (11): 1838–1847.

Blackburn EH and Collins K (2011) Telomerase: an RNP enzyme synthesizes DNA. Cold Spring Harbor Perspectives in Biology 3 (5): a003558.

Bratkovic T, Bozic J and Rogelj B (2020) Functional diversity of small nucleolar RNAs. Nucleic Acids Research 48 (4): 1627–1651.

Carthew RW and Sontheimer EJ (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell 136 (4): 642–655.

Cech TR and Steitz JA (2014) The noncoding RNA revolution‐trashing old rules to forge new ones. Cell 157 (1): 77–94.

Chang DD and Clayton DA (1989) Mouse RNAase MRP RNA is encoded by a nuclear gene and contains a decamer sequence complementary to a conserved region of mitochondrial RNA substrate. Cell 56 (1): 131–139.

Chen LL (2016) Linking long noncoding RNA localization and function. Trends in Biochemical Sciences 41 (9): 761–772.

Cramer P (2019) Eukaryotic transcription turns 50. Cell 179 (4): 808–812.

Dong P, Xiong Y, Yue J, et al. (2018) Long non‐coding RNA NEAT1: a novel target for diagnosis and therapy in human tumors. Frontiers in Genetics 9: 471.

Fire A, Xu S, Montgomery MK, et al. (1998) Potent and specific genetic interference by double‐stranded RNA in Caenorhabditis elegans. Nature 391 (6669): 806–811.

Gebert LFR and MacRae IJ (2019) Regulation of microRNA function in animals. Nature Reviews Molecular Cell Biology 20 (1): 21–37.

Ghildiyal M and Zamore PD (2009) Small silencing RNAs: an expanding universe. Nature Reviews Genetics 10 (2): 94–108.

Golden DE, Gerbasi VR and Sontheimer EJ (2008) An inside job for siRNAs. Molecular Cell 31 (3): 309–312.

Hamilton AJ and Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286 (5441): 950–952.

Hammond SM, Bernstein E, Beach D and Hannon GJ (2000) An RNA‐directed nuclease mediates post‐transcriptional gene silencing in Drosophila cells. Nature 404 (6775): 293–296.

Hartmann E and Hartmann RK (2003) The enigma of ribonuclease P evolution. Trends in Genetics: TIG 19 (10): 561–569.

Hu S, Wu J, Chen L and Shan G (2012) Signals from noncoding RNAs: unconventional roles for conventional pol III transcripts. The International Journal of Biochemistry & Cell Biology 44 (11): 1847–1851.

Huntzinger E and Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nature Reviews Genetics 12 (2): 99–110.

Iwasaki YW, Siomi MC and Siomi H (2015) PIWI‐interacting RNA: its biogenesis and functions. Annual Review of Biochemistry 84: 405–433.

Jorjani H, Kehr S, Jedlinski DJ, et al. (2016) An updated human snoRNAome. Nucleic Acids Research 44 (11): 5068–5082.

Kristensen LS, Andersen MS, Stagsted LVW, et al. (2019) The biogenesis, biology and characterization of circular RNAs. Nature Reviews Genetics 20 (11): 675–691.

Lagos‐Quintana M, Rauhut R, Lendeckel W and Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294 (5543): 853–858.

Lau NC, Lim LP, Weinstein EG and Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294 (5543): 858–862.

Lee RC and Ambros V (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294 (5543): 862–864.

Lewis SH, Quarles KA, Yang Y, et al. (2018) Pan‐arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements. Nature Ecology & Evolution 2 (1): 174–181.

Li X, Frank DN, Pace N, Zengel JM and Lindahl L (2002) Phylogenetic analysis of the structure of RNase MRP RNA in yeasts. RNA 8 (6): 740–751.

Lygerou Z, Allmang C, Tollervey D and Seraphin B (1996) Accurate processing of a eukaryotic precursor ribosomal RNA by ribonuclease MRP in vitro. Science 272 (5259): 268–270.

Mello CC and Conte D Jr (2004) Revealing the world of RNA interference. Nature 431 (7006): 338–342.

Miesen P, Girardi E and van Rij RP (2015) Distinct sets of PIWI proteins produce arbovirus and transposon‐derived piRNAs in Aedes aegypti mosquito cells. Nucleic Acids Research 43 (13): 6545–6556.

Morazzani EM, Wiley MR, Murreddu MG, Adelman ZN and Myles KM (2012) Production of virus‐derived ping‐pong‐dependent piRNA‐like small RNAs in the mosquito soma. PLoS Pathogens 8 (1): e1002470.

Morris KV and Mattick JS (2014) The rise of regulatory RNA. Nature Reviews Genetics 15 (6): 423–437.

Ozata DM, Gainetdinov I, Zoch A, O'Carroll D and Zamore PD (2019) PIWI‐interacting RNAs: small RNAs with big functions. Nature Reviews Genetics 20 (2): 89–108.

Pamudurti NR, Bartok O, Jens M, et al. (2017) Translation of CircRNAs. Molecular Cell 66 (1): 9–21.e7.

Pasquinelli AE, Reinhart BJ, Slack F, et al. (2000) Conservation of the sequence and temporal expression of let‐7 heterochronic regulatory RNA. Nature 408 (6808): 6886–6889.

Patel AA and Steitz JA (2003) Splicing double: insights from the second spliceosome. Nature Reviews Molecular Cell Biology 4 (12): 960–970.

Quinn JJ and Chang HY (2016) Unique features of long non‐coding RNA biogenesis and function. Nature Reviews Genetics 17 (1): 47–62.

Ransohoff JD, Wei Y and Khavari PA (2018) The functions and unique features of long intergenic non‐coding RNA. Nature Reviews Molecular Cell Biology 19 (3): 143–157.

Sharp PA (2005) The discovery of split genes and RNA splicing. Trends in Biochemical Sciences 30 (6): 279–281.

Tollervey D and Kiss T (1997) Function and synthesis of small nucleolar RNAs. Current Opinion in Cell Biology 9 (3): 337–342.

Uszczynska‐Ratajczak B, Lagarde J, Frankish A, Guigo R and Johnson R (2018) Towards a complete map of the human long non‐coding RNA transcriptome. Nature Reviews Genetics 19 (9): 535–548.

Volders PJ, Anckaert J, Verheggen K, et al. (2019) LNCipedia 5: towards a reference set of human long non‐coding RNAs. Nucleic Acids Research 47 (D1): D135–D139.

Wang T, Tian C, Zhang W, et al. (2007) 7SL RNA mediates virion packaging of the antiviral cytidine deaminase APOBEC3G. Journal of Virology 81 (23): 13112–13124.

Will CL and Luhrmann R (2011) Spliceosome structure and function. Cold Spring Harbor Perspectives in Biology 3 (7): a003707.

Yu CY and Kuo HC (2019) The emerging roles and functions of circular RNAs and their generation. Journal of Biomedical Science 26 (1): 29.

Zamore PD, Tuschl T, Sharp PA and Bartel DP (2000) RNAi: double‐stranded RNA directs the ATP‐dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101 (1): 25–33.

Zhang W, Du J, Yu K, et al. (2010) Association of potent human antiviral cytidine deaminases with 7SL RNA and viral RNP in HIV‐1 virions. Journal of Virology 84 (24): 12903–12913.

Zhu Y, Stribinskis V, Ramos KS and Li Y (2006) Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA. RNA 12 (5): 699–706.

Further Reading

Cech TR and Steitz JA (2014) The noncoding RNA revolution‐trashing old rules to forge new ones. Cell 157: 77–94.

Cech T, Steitz JA and Atkins JF (2018) RNA Worlds: New Tools for Deep Exploration. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY.

Cramer P (2019) Eukaryotic transcription turns 50. Cell 179 (4): 808–812.

Bratkovic T, Bozic J and Rogelj B (2020) Functional diversity of small nucleolar RNAs. Nucleic Acids Research 48 (4): 1627–1651.

Gebert LFR and MacRae IJ (2019) Regulation of microRNA function in animals. Nature Reviews Molecular Cell Biology 20 (1): 21–37.

Morris KV and Mattick JS (2014) The rise of regulatory RNA. Nature Reviews Genetics 15: 423–437.

Oeffinger M and Zenklusen D (2019) The Biology of mRNA: Structure and Function. Springer Nature: Berlin, Germany.

Sharp PA (2005) The discovery of split genes and RNA splicing. Trends in Biochemical Sciences 30 (6): 279–281.

Soll D and RajBhandary UL (1995) tRNA: Structure, Biosynthesis, and Function. ASM Press: Washington, DC.

Zimmermann RA and Dahlberg AE (1996) Ribosomal RNA Structure, Evolution, Processing, and Function in Protein Biosynthesis. CRC Press: Boca Raton, FL.

Related Sub-Topics:

RNA Structure and Function | Noncoding RNA
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Article Title: Cellular RNAs: Varied Roles
 
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Gu, Jian, and Xu, Yifan(Aug 2020) Cellular RNAs: Varied Roles. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0029149]