Review
Special Issue: Noncoding and small RNAs
Intronic noncoding RNAs and splicing

https://doi.org/10.1016/j.tplants.2008.04.010Get rights and content

The gene organization of small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs) varies within and among different organisms. This diversity is reflected in the maturation pathways of these small noncoding RNAs (ncRNAs). The presence of noncoding RNAs in introns has implications for the biogenesis of both mature small RNAs and host mRNA. The balance of the interactions between the processing or ribonucleoprotein assembly of intronic noncoding RNAs and the splicing process can regulate the levels of ncRNA and host mRNA. The processing of snoRNAs – both intronic and non-intronic – is well characterised in yeast, plants and animals and provides a basis for examining how intronic plant miRNAs are processed.

Section snippets

Noncoding RNAs in eukaryotes

The existence of noncoding RNAs (ncRNAs), such as tRNAs and rRNAs, has been known for many decades. Other small, stable RNAs are relatively well characterised and involved in, for example, splicing, ribosome biogenesis, translation and chromosome replication. These RNAs include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), RNase P and mitochondrial RNA processing (MRP) RNA, signal recognition particle (SRP) RNA, and telomerase RNA (see Glossary for list of RNA species discussed

snoRNAs and their gene organization

The two major classes of snoRNA (box C/D and box H/ACA snoRNAs; see Glossary) are responsible for directing 2′-O-ribose methylation and pseudouridylation of target RNAs, most commonly rRNA and snRNAs. snoRNAs of each class associate with different sets of core proteins to form small nucleolar ribonucleoprotein particles (snoRNPs), which function in modification 5, 6, 7. The organization of snoRNA genes is extremely diverse, both within and among different eukaryotes (Figure 1) [7]. The majority

miRNAs and their gene organization

miRNAs are small ncRNAs of approximately 21–23 nt in length. They regulate gene expression at the post-transcriptional level in animals and plants by base-pairing to target mRNAs 1, 17, 18, 19, 20, 21. miRNAs are produced from primary miRNA (pri-miRNA) transcripts, which fold to form extensively double-stranded stem–loop structures. In animals, processing of the pri-miRNA by the RNase III Drosha occurs in the nucleus and produces an intermediate precursor miRNA (pre-miRNA), which is then

Splicing and intronic snoRNAs

As described above, intron sequences sometimes contain miRNAs and snoRNAs with extensive secondary structures that are recognized by proteins or assemble proteins to form RNPs. The existence of such sequences raises the question of whether RNA folding or RNP formation affects the splicing process or vice versa. Secondary structures in plant and animal introns can affect both splicing efficiency and splice-site selection 41, 42, 43, and therefore snoRNAs or pri-miRNAs have the potential to

Splicing and intronic miRNAs

In animals, several routes for the generation of pri-miRNAs from introns in pre-mRNAs have been described. Processing might occur in a manner that is essentially the same as the processing of intronic snoRNAs, wherein the pri-miRNA is released from the excised and linearised intron lariat (Figure 1a). Alternatively, Drosha might cleave the pre-miRNA from the excised lariat, from the linearised intron or, indeed, from the unspliced pre-mRNA (Figure 1c). Drosha-mediated cleavage of the pri-mRNA

Acknowledgements

This work was supported by the Scottish Government (to J.B. and D.F.M.), the CNRS and L’Agence Nationale de la Recherché (ANR) Blanc project Osmir (to M.E.), and the European Alternative Splicing Network of Excellence (EURASNET) (to J.B.).

Glossary

Box C/D
Box C/D snoRNAs contain conserved sequences: box C (GUGAUGA) and D (CUGA), near their 5′ and 3′ ends, respectively.
Box H/ACA
Box H/ACA snoRNAs fold into two stem–loop structures in the 5′ and 3′ halves of the RNA. These structures are adjacent to the conserved internal box H (ANANNA) and the 3′-terminal box ACA (ACANNN).
miRNAs
microRNAs, small regulatory RNAs.
ncRNA
noncoding RNA, does not code for protein.
pre-miRNA
precursor miRNA transcript produced by initial processing of pri-miRNA by

References (63)

  • R.S. Pillai

    Repression of protein synthesis by miRNAs: how many mechanisms

    Trends Cell Biol.

    (2007)
  • S.N. Bhattacharyya

    Relief of microRNA-mediated translational repression in human cells subjected to stress

    Cell

    (2006)
  • A.K.L. Leung et al.

    microRNAs: a safeguard against turmoil?

    Cell

    (2007)
  • R. Sunkar

    Small RNAs are big players in plant abiotic stress responses and nutrient deprivation

    Trends Plant Sci.

    (2007)
  • T. Hirose

    Splicing-dependent and independent modes of assembly for intron-encoded box C/D snoRNAs in mammalian cells

    Mol. Cell

    (2003)
  • T. Hirose

    A spliceosomal intron binding protein, IBP160, links position-dependent assembly of intron-encoded box C/D snoRNP to pre-mRNA splicing

    Mol. Cell

    (2006)
  • Z. Xie

    Negative feedback regulation of Dicer-like1 in Arabidopsis by microRNA-guided mRNA degradation

    Curr. Biol.

    (2003)
  • D.J. Leader

    U14snoRNAs of the fern, Asplenium nidus, contain large sequence insertions compared with those of higher plants

    Biochim. Biophys. Acta

    (1998)
  • G. Storz

    An abundance of RNA regulators

    Annu. Rev. Biochem.

    (2005)
  • J.S. Mattick et al.

    Non-coding RNA

    Hum. Mol. Genet.

    (2006)
  • H. Kawaji et al.

    Exploration of small RNAs

    PLoS Genet.

    (2008)
  • J.P. Bachellerie

    Nucleotide modifications of eukaryotic rRNAs: the world of small nucleolar RNA guides revisited

  • Z.-P. Huang

    Genome-wide analyses of two families of snoRNA genes from Drosophila melanogaster, demonstrating the extensive utilisation of introns for coding of snoRNAs

    RNA

    (2005)
  • D.J. Leader

    Clusters of multiple different small nucleolar RNA genes in plants are expressed as and processed from polycistronic pre-snoRNAs

    EMBO J.

    (1997)
  • L.-H. Qu

    Seven novel methylation guide small nucleolar RNAs are processed from a common polycistronic transcript by Rat1p and RNase III in yeast

    Mol. Cell. Biol.

    (1999)
  • P. Comella

    Characterization of a ribonuclease III-like protein required for cleavage of the pre-rRNA in the 3′ETS in Arabidopsis

    Nucleic Acids Res.

    (2008)
  • C.L. Chen

    The high diversity of snoRNAs in plants: identification and comparative study of 120 snoRNA genes from Oryza sativa

    Nucleic Acids Res.

    (2003)
  • D.J. Leader

    Splicing-independent processing of plant box C/D and box H/ACA small nucleolar RNAs

    Plant Mol. Biol.

    (1999)
  • V.N. Kim

    microRNA biogenesis: coordinated cropping and dicing

    Nat. Rev. Mol. Cell Biol.

    (2005)
  • M.W. Jones-Rhoades

    microRNAs and their regulatory roles in plants

    Annu. Rev. Plant Biol.

    (2006)
  • A.C. Mallory et al.

    Functions of microRNAs and related small RNAs in plants

    Nat. Genet.

    (2006)

    • Cited by (117)

    • The emerging diagnostic and therapeutic roles of small nucleolar RNAs in lung diseases

      2023, Biomedicine and Pharmacotherapy

    • Introns: Good Day Junk Is Bad Day Treasure

      2019, Trends in Genetics

    • Long non-coding RNA: Classification, biogenesis and functions in blood cells

      2019, Molecular Immunology
      Citation Excerpt :

      Non-coding RNAs (ncRNAs) are found to deliver housekeeping functions in several biological processes by taking part in the regulatory mechanism of gene expression at the transcriptional and post-transcriptional level (Palazzo and Lee, 2015; Mattick and Makunin, 2006; Esteller, 2011). The lncRNA sequence may be present as introns and intergenic region in the same set of genes that encode proteins (Brown et al., 2008; Deveson et al., 2017). Two decades back the discovery of small ncRNA opened the avenues for the existence of other functional ncRNAs.

    • Box C/D snoRNP Autoregulation by a cis-Acting snoRNA in the NOP56 Pre-mRNA

      2018, Molecular Cell
      Citation Excerpt :

      Excised and debranched introns are normally degraded by exonucleases, but snoRNP or pre-snoRNP formation protects the snoRNA. The “byproduct” from this production scheme is a spliced transcript, either a mRNA or a lncRNA, which may or may not be functional (Brown et al., 2008; Dupuis-Sandoval et al., 2015). We, and others, have demonstrated that snoRNA host genes are particularly disposed to producing alternatively spliced transcript variants that are subjected to degradation by the cytoplasmic nonsense-mediated decay (NMD) pathway (Colombo et al., 2017; Lykke-Andersen et al., 2014; Thoren et al., 2010; Weischenfeldt et al., 2008).

    • Engineering Introns to Express RNA Guides for Cas9- and Cpf1-Mediated Multiplex Genome Editing

      2018, Molecular Plant

    • SNORA73B promotes endometrial cancer progression through targeting MIB1 and regulating host gene RCC1 alternative splicing

      2023, Journal of Cellular and Molecular Medicine
    View all citing articles on Scopus
    View full text
    Copyright © 2008 Elsevier Ltd. All rights reserved.