Cellular RNAs: Varied Roles

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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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.

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

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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.

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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]