Skip to main content
SpringerLink
Log in

On the Possibility of an Early Evolutionary Origin for the Spliced Leader Trans-Splicing

  • Original Article
  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Trans-splicing is a process by which 5′- and 3′-ends of two pre-RNA molecules transcribed from different sites of the genome can be joined together to form a single RNA molecule. The spliced leader (SL) trans-splicing is mediated by the spliceosome and it allows the replacement of 5′-end of pre-mRNA by 5′(SL)-end of SL-RNA. This form of splicing has been observed in many phylogenetically unrelated eukaryotes. Either the SL trans-splicing (SLTS) originated in the last eukaryotic common ancestor (LECA) (or even earlier) and it was lost in most eukaryotic lineages, or this mechanism of RNA processing evolved several times independently in various unrelated eukaryotic taxa. The bioinformatic comparisons of SL-RNAs from various eukaryotic taxonomic groups have revealed the similarities of secondary structures of most SL-RNAs and a relative conservation of their splice sites (SSs) and Sm-binding sites (SmBSs). We propose that such structural and functional similarities of SL-RNAs are unlikely to have evolved repeatedly many times. Hence, we favor the scenario of an early evolutionary origin for the SLTS and multiple losses of SL-RNAs in various eukaryotic lineages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

LECA:

The last eukaryotic common ancestor

LUCA:

The last universal common ancestor

Sm:

“Smith antigen” proteins which bind to small nuclear RNAs (snRNAs), i.e., spliceosomal U (U-rich) or SL snRNAs

SmBS:

Sm-binding site

SL:

Capped spliced leader sequence which is transferred to 5′-end of pre-mRNA during SL trans-splicing

SL-RNA:

Spliced leader (SL) snRNA which serves as donor of capped SL sequences for pre-mRNA

SLTS:

Spliced leader trans-splicing

SS:

Splice site

References

  • Allen MA, Hillier LW, Waterston RH, Blumenthal T (2011) A global analysis of C. elegans trans-splicing. Genome Res 21:255–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bangs JD, Crain PF, Hashizume T, McCloskey JA, Boothroyd JC (1992) Mass spectrometry of mRNA cap 4 from trypanosomatids reveals two novel nucleosides. J Biol Chem 267:9805–9815

    CAS  PubMed  Google Scholar 

  • Bartschat S, Samuelsson T (2010) U12 type introns were lost at multiple occasions during evolution. BMC Genom 11:106

    Article  Google Scholar 

  • Beauparlant MA, Drouin G (2014) Multiple independent insertions of 5S rRNA genes in the spliced-leader gene family of trypanosome species. Curr Genet 60:17–24

    Article  CAS  PubMed  Google Scholar 

  • Berriman M, Ghedin E, Hertz-Fowler C et al (2005) The genome of the african trypanosome Trypanosoma brucei. Science 309:416–422

    Article  CAS  PubMed  Google Scholar 

  • Bitar M, Boroni M, Macedo AM, Machado CR, Franco GR (2013) The spliced leader trans-splicing mechanism in different organisms: molecular details and possible biological roles. Front Genet 4:199

    Article  PubMed  PubMed Central  Google Scholar 

  • Blaxter M, Liu L (1996) Nematode spliced leaders—ubiquity, evolution and utility. Int J Parasitol 26:1025–1033

    CAS  PubMed  Google Scholar 

  • Blumenthal T (2004) Operons in eukaryotes. Brief Funct Genomic Proteom 3:199–211

    Article  CAS  Google Scholar 

  • Blumenthal T (2012) Trans-splicing and operons in C. elegans. WormBook. 2012 Nov 20:1–11. doi: 10.1895/wormbook.1.5.2

  • Blumenthal T, Davis P,Garrido-Lecca A (2015) Operon and non-operon gene clusters in the C. elegans genome (April 28, 2015). WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.175.1, http://www.wormbook.org

  • Brehm K, Jensen K, Frosch M (2000) mRNA trans-splicing in the human parasitic cestode Echinococcus multilocularis. J Biol Chem 275:38311–38318

    Article  CAS  PubMed  Google Scholar 

  • Bruzik JP, Steitz JA (1990) Spliced leader RNA sequences can substitute for the essential 5′ end of U1 RNA during splicing in a mammalian in vitro system. Cell 62:889–899

    Article  CAS  PubMed  Google Scholar 

  • Bruzik JP, Doren KV, Hirsh D, Steitz JA (1988) Trans splicing involves a novel form of small nuclear ribonucleoprotein particles. Nature 335:559–562

    Article  CAS  PubMed  Google Scholar 

  • Campbell DA, Thomas S, Sturm NR (2003) Transcription in kinetoplastid protozoa: why be normal? Microbes Infect 5:1231–1240

    Article  CAS  PubMed  Google Scholar 

  • Darty K, Denise A, Ponty Y (2009) VARNA: Interactive drawing and editing of the RNA secondary structure. Bioinformatics 25:1974–1975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis RE (1996) Spliced leader RNA trans-splicing in metazoa. Parasitol Today 12:33–40

    Article  CAS  PubMed  Google Scholar 

  • Davis RE (1997) Surprising diversity and distribution of spliced leader RNAs in flatworms. Mol Biochem Parasitol 87:29–48

    Article  CAS  PubMed  Google Scholar 

  • Davis RE, Hardwick C, Tavernier P, Hodgson S, Singh H (1995) RNA Trans-splicing in flatworms. Analysis of trans-spliced mRNAs and genes in the human parasite Schistosoma mansoni. J Biol Chem 270:21813–21819

    Article  CAS  PubMed  Google Scholar 

  • Denker JA, Zuckerman DM, Maroney PA, Nilsen TW (2002) New components of the spliced leader RNP required for nematode trans-splicing. Nature 417:667–670

    Article  CAS  PubMed  Google Scholar 

  • Derelle R, Momose T, Manuel M, Da Silva C, Wincker P, Houliston E (2010) Convergent origins and rapid evolution of spliced leader trans-splicing in Metazoa: Insights from the Ctenophora and Hydrozoa. RNA 16:696–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doren KV, Hirsh D (1988) Trans-spliced leader RNA exists as small nuclear ribonucleoprotein particles in Caenorhabditis elegans. Nature 335:556–559

    Article  PubMed  Google Scholar 

  • Douris V, Telford MJ, Averof M (2010) Evidence for multiple independent origins of trans-splicing in Metazoa. Mol Biol Evol 27:684–693

    Article  CAS  PubMed  Google Scholar 

  • Drouin G, Tsang C (2012) 5S rRNA gene arrangements in protists: a case of nonadaptive evolution. J Mol Evol 74:342–351

    Article  CAS  PubMed  Google Scholar 

  • Ebel C, Frantz C, Paulus F, Imbault P (1999) Trans-splicing and cis-splicing in the colourless Euglenoid, Entosiphon sulcatum. Curr Genet 35:542–550

    Article  CAS  PubMed  Google Scholar 

  • Evans D, Blumenthal T (2000) trans splicing of polycistronic Caenorhabditis elegans pre-mRNAs: analysis of the SL2 RNA. Mol Cell Biol 20:6659–6667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans D, Zorio D, MacMorris M, Winter CE, Lea K, Blumenthal T (1997) Operons and SL2 trans-splicing exist in nematodes outside the genus Caenorhabditis. Proc Natl Acad Sci USA 94:9751–9756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganot P, Kallesøe T, Reinhardt R, Chourrout D, Thompson EM (2004) Spliced-leader RNA trans splicing in a chordate, Oikopleura dioica, with a compact genome. Mol Cell Biol 24:7795–7805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gibson W, Bingle L, Blendeman W, Brown J, Wood J, Stevens J (2000) Structure and sequence variation of the trypanosome spliced leader transcript. Mol Biochem Parasitol 107:269–277

    Article  CAS  PubMed  Google Scholar 

  • Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41:95–98

    CAS  Google Scholar 

  • Hannon GJ, Maroney PA, Nilsen TW (1991) U small nuclear ribonucleoprotein requirements for nematode cis- and trans-splicing in vitro. J Biol Chem 266:22792–22795

    CAS  PubMed  Google Scholar 

  • Harris KA, Crothers DM, Ullu E (1995) In vivo structural analysis of spliced leader RNAs in Trypanosoma brucei and Leptomonas collosoma: a flexible structure that is independent of cap4 methylations. RNA 1:351–362

    CAS  PubMed  PubMed Central  Google Scholar 

  • Harrison N, Kalbfleisch A, Connolly B, Pettitt J, Müller B (2010) SL2-like spliced leader RNAs in the basal nematode Prionchulus punctatus: New insight into the evolution of nematode SL2 RNAs. RNA 16:1500–15007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hastings KEM (2005) SL trans-splicing: easy come or easy go? Trends Genet 21:240–247

    Article  CAS  PubMed  Google Scholar 

  • Hofacker IL, Fekete M, Stadler PF (2002) Secondary structure prediction for aligned RNA sequences. J Mol Biol 319:1059–1066

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Bachvaroff TR, Handy SM, Delwiche CF (2011) Dynamics of actin evolution in dinoflagellates. Mol Biol Evol 28:1469–1480

    Article  CAS  PubMed  Google Scholar 

  • Koehl P (2001) Protein structure similarities. Curr Opinion Struct Biol 11:348–353

    Article  CAS  Google Scholar 

  • Lasda EL, Blumenthal T (2011) Trans-splicing. Wiley Interdiscip Rev. RNA 2:417–434

    CAS  PubMed  Google Scholar 

  • LeCuyer KA, Crothers DM (1993) The Leptomonas collosoma spliced leader RNA can switch between two alternate structural forms. Biochemistry 32:5301–5311

    Article  CAS  PubMed  Google Scholar 

  • Liang XH, Haritan A, Uliel S, Michaeli S (2003) trans and cis splicing in trypanosomatids: mechanism, factors, and regulation. Eukaryot Cell 2:830–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lidie KB, van Dolah FM (2007) Spliced leader RNA-mediated trans-splicing in a dinoflagellate, Karenia brevis. J Eukaryot Microbiol 54:427–435

    Article  CAS  PubMed  Google Scholar 

  • Lin CF, Mount SM, Jarmołowski A, Makałowski W (2010) Evolutionary dynamics of U12-type spliceosomal introns. BMC Evol Biol 10:47

    Article  PubMed  PubMed Central  Google Scholar 

  • Lorenz R, Bernhart S, Honer zu Siederdissen C, Tafer H, Flamm C, Stadler P, Hofacker I (2011) ViennaRNA Package 2.0. Algorithms Mol Biol 6:26

  • Marlétaz F, Gilles A, Caubit X, Perez Y, Dossat C, Samain S, Gyapay G, Wincker P, Le Parco Y (2008) Chaetognath transcriptome reveals ancestral and unique features among bilaterians. Genome Biol 9:R94

    Article  PubMed  PubMed Central  Google Scholar 

  • Maroney PA, Hannon GJ, Shambaugh JD, Nilsen TW (1991) Intramolecular base pairing between the nematode spliced leader and its 5′ splice site is not essential for trans-splicing in vitro. EMBO J 10:3869–3875

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maroney PA, Denker JA, Darzynkiewicz E, Laneve R, Nilsen TW (1995) Most mRNAs in the nematode Ascaris lumbricoides are trans-spliced: a role for spliced leader addition in translational efficiency. RNA 1:714–723

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maroney PA, Yu YT, Jankowska M, Nilsen TW (1996) Direct analysis of nematode cis- and trans-spliceosomes: a functional role for U5 snRNA in spliced leader addition trans-splicing and the identification of novel Sm snRNPs. RNA 2:735–745

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marz M, Vanzo N, Stadler PF (2010) Temperature-dependent structural variability of RNAs: spliced leader RNAs and their evolutionary history. J Bioinf Comput Biol 8:1–17

    Article  CAS  Google Scholar 

  • Mateášiková-Kováčová B, Vesteg M, Drahovská H, Záhonová K, Vacula R, Krajčovič J (2012) Nucleus-encoded mRNAs for chloroplast proteins GapA, PetA, and PsbO are trans-spliced in the flagellate Euglena gracilis irrespective of light and plastid function. J Eukaryot Microbiol 59:651–653

    Article  PubMed  Google Scholar 

  • Matera AG, Wang Z (2014) A day in the life of the spliceosome. Nat Rev Mol Cell Biol 15:108–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller SI, Landfear SM, Wirth DF (1986) Cloning and characterization of a Leishmania gene encoding a RNA spliced leader sequence. Nucl Acids Res 14:7341–7360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muhich ML, Hughes DE, Simpson AM, Simpson L (1987) The monogenetic kinetoplastid protozoan, Crithidia fasciculata, contains a transcriptionally active, multicopy mini-exon sequence. Nucl Acids Res 15:3141–3153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nilsen TW (1993) Trans-splicing of nematode premessenger RNA. Annu Rev Microbiol 47:413–440

    Article  CAS  PubMed  Google Scholar 

  • Nilsen TW (1995) trans-splicing: an update. Mol Biochem Parasitol 73:1–6

    Article  CAS  PubMed  Google Scholar 

  • Nilsen TW (2001) Evolutionary origin of SL-addition trans-splicing: still an enigma. Trends Genet 17:678–680

    Article  CAS  PubMed  Google Scholar 

  • Nowack ECM, Price DC, Bhattacharya D, Singer A, Melkonian M, Grossman AR (2016) Gene transfers from diverse bacteria compensate for reductive genome evolution in the chromatophore of Paulinella chromatophora. Proc Natl Acad Sci USA 113:12214–12219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palfi Z, Schimanski B, Güntze A, Lücke S, Bindereif A (2005) U1 small nuclear RNP from Trypanosoma brucei: a minimal U1 snRNA with unusual protein components. Nucl Acids Res 8:2493–2503

    Article  Google Scholar 

  • Pouchkina-Stantcheva NN, Tunnacliffe A (2005) Spliced leader RNA-mediated trans-splicing in phylum Rotifera. Mol Biol Evol 22:1482–1489

    Article  CAS  PubMed  Google Scholar 

  • Protasio AV, Tsai IJ, Babbage A et al (2012) A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni. PLoS Negl Trop Dis 6:e1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajkovic A, Davis RE, Simonsen JN, Rottman FM (1990) A spliced leader is present on a subset of mRNAs from the human parasite Schistosoma mansoni. Proc Natl Acad Sci USA 87:8879–8883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rossi A, Ross EJ, Jack A, Sánchez Alvarado A (2014) Molecular cloning and characterization of SL3: a stem cell-specific SL RNA from the planarian Schmidtea mediterranea. Gene 533:156–167

    Article  CAS  PubMed  Google Scholar 

  • Roy SW (2017) Genomic and transcriptomic analysis reveals spliced leader trans-splicing in cryptomonads. Genome Biol Evol 9:468–473

    Article  PubMed  Google Scholar 

  • Russell AG, Charette JM, Spencer DF, Gray MW (2006) An early evolutionary origin for the minor spliceosome. Nature 443:863–866

    Article  CAS  PubMed  Google Scholar 

  • Siebert S, Backofen R (2005) MARNA: multiple alignment and consensus structure prediction of RNAs based on sequence structure comparisons. Bioinformatics 21:3352–3359

    Article  CAS  PubMed  Google Scholar 

  • Siegel TN, Hekstra DR, Wang X, Dewell S, Cross GAM (2010) Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucl Acids Res 38:4946–4957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins DG (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539

    Article  PubMed  PubMed Central  Google Scholar 

  • Stover NA, Steele RE (2001) Trans-spliced leader addition to mRNAs in a cnidarian. Proc Natl Acad Sci USA 98:5693–5698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stover NA, Kaye MS, Cavalcanti ARO (2006) Spliced leader trans-splicing. Curr Biol 16:R8–R9

    Article  CAS  PubMed  Google Scholar 

  • Sturm NR, Yu MC, Campbell DA (1999) Transcription termination and 3′-end processing of the spliced leader RNA in kinetoplastids. Mol Cell Biol 19:1595–1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas JD, Conrad RC, Blumenthal T (1988) The C. elegans trans-spliced leader RNA is bound to Sm and has a trimethylguanosine cap. Cell 54:533–539

    Article  CAS  PubMed  Google Scholar 

  • Torarinsson E, Lindgreen S (2008) WAR: Webserver for aligning structural RNAs. Nucleic Acids Res 36:W79–W84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Doren K, Hirsh D (1990) mRNAs that mature through trans-splicing in Caenorhabditis elegans have a trimethylguanosine cap at their 5′ termini. Mol Cell Biol 10:1769–1772

    Article  PubMed  PubMed Central  Google Scholar 

  • Vesteg M, Krajčovič J (2011) The falsifiability of the models for the origin of eukaryotes. Curr Genet 57:367–390

    Article  CAS  PubMed  Google Scholar 

  • Vesteg M, Vacula R, Burey S, Löffelhardt W, Drahovská H, Martin W, Krajčovič J (2009) Expression of nucleus-encoded genes for chloroplast proteins in the flagellate Euglena gracilis. J Eukaryot Microbiol 56:159–166

    Article  CAS  PubMed  Google Scholar 

  • Vesteg M, Vacula R, Steiner JM, Mateášiková B, Löffelhardt W, Brejová B, Krajčovič J (2010) A possible role for short introns in the acquisition of stroma-targeting peptides in the flagellate Euglena gracilis. DNA Res 17:223–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vesteg M, Šándorová Z, Krajčovič J (2012) Selective forces for the origin of spliceosomes. J Mol Evol 74:226–231

    Article  CAS  PubMed  Google Scholar 

  • Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ (2009) Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189–1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang F, Xu D, Zhuang Y et al (2015) Spliced leader RNA trans-splicing discovered in copepods. Sci Rep 5:17411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeats B, Matsumoto J, Mortimer SI, Shoguchi E, Satoh N, Hastings KE (2010) SL RNA genes of the ascidian tunicates Ciona intestinalis and Ciona savignyi. Zool Sci 27:171–180

    Article  CAS  PubMed  Google Scholar 

  • Yu YT, Maroney PA, Nilsen TW (1993) Functional reconstitution of U6 snRNA in nematode cis- and trans-splicing: u6 can serve as both a branch acceptor and a 5′ exon. Cell 75:1049–1059

    Article  CAS  PubMed  Google Scholar 

  • Zayas RM, Bold TD, Newmark PA (2005) Spliced-leader trans-splicing in freshwater planarians. Mol Biol Evol 22:2048–2054

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Hou Y, Miranda L, Campbell DA, Sturm NR, Gaasterland T, Lin S (2007) Spliced leader RNA trans-splicing in dinoflagellates. Proc Nat Acad Sci USA 104:4618–4623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Campbell DA, Sturm NR, Lin S (2009) Dinoflagellate spliced leader RNA genes display a variety of sequences and genomic arrangements. Mol Biol Evol 26:1757–1771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Campbell DA, Sturm NR, Dungan CF, Lin S (2011) Spliced leader RNAs, mitochondrial gene frameshifts and multi-protein phylogeny expand support for the genus Perkinsus as a unique group of alveolates. PLoS ONE 6:e19933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucl Acids Res 31:3406–3415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Scientific Grant Agency of the Slovak Ministry of Education and the Academy of Sciences (Grants VEGA 1/0626/13 and 1/0535/17), and by project ITMS 26210120024 supported by the Research & Development Operational Programme funded by the ERDF.

Author information

Authors and Affiliations

  1. Department of RNA Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Zuzana Krchňáková

  2. Department of Biology, Faculty of Natural Sciences, University of ss. Cyril and Methodius, Trnava, Slovakia

    Juraj Krajčovič

  3. Department of Biology and Ecology, Faculty of Natural Sciences, Matej Bel University, Tajovského 40, 974 01, Banská Bystrica, Slovakia

    Matej Vesteg

Authors
  1. Zuzana Krchňáková
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juraj Krajčovič
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matej Vesteg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matej Vesteg.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krchňáková, Z., Krajčovič, J. & Vesteg, M. On the Possibility of an Early Evolutionary Origin for the Spliced Leader Trans-Splicing. J Mol Evol 85, 37–45 (2017). https://doi.org/10.1007/s00239-017-9803-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-017-9803-y

Keywords

Search

Navigation