spliced leader rna


Summary: The small RNAs which provide spliced leader sequences, SL1, SL2, SL3, SL4 and SL5 (short sequences which are joined to the 5' ends of pre-mRNAs by TRANS-SPLICING). They are found primarily in primitive eukaryotes (protozoans and nematodes).

Top Publications

  1. Xu P, Wen L, Benegal G, Wang X, Buck G. Identification of a spliced leader RNA binding protein from Trypanosoma cruzi. Mol Biochem Parasitol. 2001;112:39-49 pubmed
    ..Finally, UV cross-linking SL RNA with S100 extract indicated native XB1 protein and SL RNA interaction in T. cruzi extract...
  2. Lidie K, Van Dolah F. Spliced leader RNA-mediated trans-splicing in a dinoflagellate, Karenia brevis. J Eukaryot Microbiol. 2007;54:427-35 pubmed
    ..brevis occurs via a trans-splicing process in which a common SL sequence is added to the 5'-end of mature mRNAs. The occurrence of SL trans-splicing in a dinoflagellate extends the known phylogenetic range of this process. ..
  3. Dollet M, Sturm N, Campbell D. The spliced leader RNA gene array in phloem-restricted plant trypanosomatids (Phytomonas) partitions into two major groupings: epidemiological implications. Parasitology. 2001;122:289-97 pubmed
    ..phytomonads and the variability within groups, the exon, intron and non-transcribed spacer sequences of the spliced leader RNA gene were compared among isolates of the phloem-restricted members...
  4. Biton M, Mandelboim M, Arvatz G, Michaeli S. RNAi interference of XPO1 and Sm genes and their effect on the spliced leader RNA in Trypanosoma brucei. Mol Biochem Parasitol. 2006;150:132-43 pubmed publisher
    ..that involves the addition of a spliced leader sequence to all mRNAs from a small RNA species, known as the spliced leader RNA (SL RNA)...
  5. Cribb P, Tapia E, Diosque P, Serra E. Spliced leader RNA gene promoter sequence heterogeneity in CL-Brener Trypanosoma cruzi reference strain. Infect Genet Evol. 2004;4:153-7 pubmed
    ..cruzi I origin into a T. cruzi II strain. The possible origins of these sequences are discussed. ..
  6. Campbell D, Sturm N, Yu M. Transcription of the kinetoplastid spliced leader RNA gene. Parasitol Today. 2000;16:78-82 pubmed
    ..In this article, David Campbell, Nancy Sturm and Michael Yu review the field of kinetoplastid SL RNA gene transcription, address past proposals in light of current data and discuss some of the differences that appear in the literature. ..
  7. Arhin G, Ullu E, Tschudi C. 2'-O-methylation of position 2 of the trypanosome spliced leader cap 4 is mediated by a 48 kDa protein related to vaccinia virus VP39. Mol Biochem Parasitol. 2006;147:137-9 pubmed publisher
  8. Thomas S, Yu M, Sturm N, Campbell D. A non-universal transcription factor? The Leishmania tarentolae TATA box-binding protein LtTBP associates with a subset of promoters. Int J Parasitol. 2006;36:1217-26 pubmed
    In kinetoplastids a 39-nucleotide spliced leader RNA is trans-spliced to the 5' end of nuclear mRNAs before they can be translated, thus the spliced leader is central to gene expression in kinetoplastid biology...
  9. Liang X, Liu Q, Liu L, Tschudi C, Michaeli S. Analysis of spliceosomal complexes in Trypanosoma brucei and silencing of two splicing factors Prp31 and Prp43. Mol Biochem Parasitol. 2006;145:29-39 pubmed
    ..We identified a 45S complex carrying pre-mRNA and all the U-snRNAs, including U1 and the SL RNA, suggesting that a single spliceosomal complex may potentially conduct both trans- and cis-splicing. ..

More Information


  1. Thomas S, Westenberger S, Campbell D, Sturm N. Intragenomic spliced leader RNA array analysis of kinetoplastids reveals unexpected transcribed region diversity in Trypanosoma cruzi. Gene. 2005;352:100-8 pubmed
    The spliced leader RNA gene (SL RNA) repeat is present in large multicopy arrays and has been used as a marker for the diversity of kinetoplastid protozoans...
  2. Zamudio J, Mittra B, Zeiner G, Feder M, Bujnicki J, Sturm N, et al. Complete cap 4 formation is not required for viability in Trypanosoma brucei. Eukaryot Cell. 2006;5:905-15 pubmed
    ..As mature cap 4 is dispensable for translation, cap 1 modifications and/or SL sequences are implicated in ribosomal interaction. ..
  3. Westenberger S, Sturm N, Yanega D, Podlipaev S, Zeledon R, Campbell D, et al. Trypanosomatid biodiversity in Costa Rica: genotyping of parasites from Heteroptera using the spliced leader RNA gene. Parasitology. 2004;129:537-47 pubmed
    ..This study reveals only a minor fraction of the trypanosomatid biodiversity, which is anticipated to be high...
  4. Lall S, Friedman C, Jankowska Anyszka M, Stepinski J, Darzynkiewicz E, Davis R. Contribution of trans-splicing, 5' -leader length, cap-poly(A) synergism, and initiation factors to nematode translation in an Ascaris suum embryo cell-free system. J Biol Chem. 2004;279:45573-85 pubmed
  5. Ganot P, Kallesøe T, Reinhardt R, Chourrout D, Thompson E. Spliced-leader RNA trans splicing in a chordate, Oikopleura dioica, with a compact genome. Mol Cell Biol. 2004;24:7795-805 pubmed
    ..Remarkably, intercistronic regions in O. dioica are far more reduced than those in either nematodes or kinetoplastids, implying minimal cis-regulatory elements for coupling of 3'-end formation and trans splicing. ..
  6. Zamudio J, Mittra B, Foldynova Trantirkova S, Zeiner G, Lukes J, Bujnicki J, et al. The 2'-O-ribose methyltransferase for cap 1 of spliced leader RNA and U1 small nuclear RNA in Trypanosoma brucei. Mol Cell Biol. 2007;27:6084-92 pubmed
    ..Accumulation of 3'-extended SL RNA substrate indicates a delay in processing and suggests a synergistic role for cap 1 in maturation. ..
  7. Evans D, Perez I, MacMorris M, Leake D, Wilusz C, Blumenthal T. A complex containing CstF-64 and the SL2 snRNP connects mRNA 3' end formation and trans-splicing in C. elegans operons. Genes Dev. 2001;15:2562-71 pubmed
    ..These results provide a molecular framework for the coupling of 3' end formation and trans-splicing in the processing of polycistronic pre-mRNAs from C. elegans operons. ..
  8. Hury A, Goldshmidt H, Tkacz I, Michaeli S. Trypanosome spliced-leader-associated RNA (SLA1) localization and implications for spliced-leader RNA biogenesis. Eukaryot Cell. 2009;8:56-68 pubmed publisher
    ..These results demonstrate that SLA1 is a unique chaperonic RNA that functions during the early biogenesis of SL RNA to maintain a structure that is most probably suitable for cap 4 modification. ..
  9. Mandelboim M, Estraño C, Tschudi C, Ullu E, Michaeli S. On the role of exon and intron sequences in trans-splicing utilization and cap 4 modification of the trypanosomatid Leptomonas collosoma SL RNA. J Biol Chem. 2002;277:35210-8 pubmed
    ..This study, however, did not provide support for the putative SL RNA-U6 small nuclear RNA (snRNA) interaction at the Sm site like in the nematodes, suggesting differences in the bridging role of U6 in the two trans-splicing systems. ..
  10. Ruan J, Shen S, Ullu E, Tschudi C. Evidence for a capping enzyme with specificity for the trypanosome spliced leader RNA. Mol Biochem Parasitol. 2007;156:246-54 pubmed
    ..Furthermore, consistent with co-transcriptional addition of the m(7)G cap, chromatin immunoprecipitation revealed recruitment of TbCgm1 to the SL RNA genes. ..
  11. Das A, Zhang Q, Palenchar J, Chatterjee B, Cross G, Bellofatto V. Trypanosomal TBP functions with the multisubunit transcription factor tSNAP to direct spliced-leader RNA gene expression. Mol Cell Biol. 2005;25:7314-22 pubmed
    ..These findings provide the first view of the architecture of a transcriptional complex that assembles at an RNA polymerase II-dependent gene promoter in a highly divergent eukaryote. ..
  12. Goyal K, Browne J, Burnell A, Tunnacliffe A. Dehydration-induced tps gene transcripts from an anhydrobiotic nematode contain novel spliced leaders and encode atypical GT-20 family proteins. Biochimie. 2005;87:565-74 pubmed
    ..avenae are upregulated, but exposure to cold or increased osmolarity also results in gene induction, although to a lesser extent. Trehalose seems likely therefore to play a role in a number of stress responses in nematodes. ..
  13. Dossin F, Schenkman S. Actively transcribing RNA polymerase II concentrates on spliced leader genes in the nucleus of Trypanosoma cruzi. Eukaryot Cell. 2005;4:960-70 pubmed
    ..The same RNA polymerase II also transcribes the genes coding for the spliced leader RNA, which are capped, exported to the cytoplasm, processed, and reimported into the nucleus before they are ..
  14. Pouchkina Stantcheva N, Tunnacliffe A. Spliced leader RNA-mediated trans-splicing in phylum Rotifera. Mol Biol Evol. 2005;22:1482-9 pubmed
  15. Li H, Tschudi C. Novel and essential subunits in the 300-kilodalton nuclear cap binding complex of Trypanosoma brucei. Mol Cell Biol. 2005;25:2216-26 pubmed publisher
    ..The cap 4 becomes part of the mRNA through trans-splicing of a 39-nucleotide-long sequence donated by the spliced leader RNA. Although the cap 4 modifications are required for trans-splicing to occur, the underlying mechanism remains ..
  16. Zhang H, Campbell D, Sturm N, Lin S. Dinoflagellate spliced leader RNA genes display a variety of sequences and genomic arrangements. Mol Biol Evol. 2009;26:1757-71 pubmed publisher
  17. Satou Y, Hamaguchi M, Takeuchi K, Hastings K, Satoh N. Genomic overview of mRNA 5'-leader trans-splicing in the ascidian Ciona intestinalis. Nucleic Acids Res. 2006;34:3378-88 pubmed
    ..An interesting feature of the Ciona polycistronic transcription units is that the great majority entirely lack intercistronic sequences. ..
  18. Zamudio J, Mittra B, Chattopadhyay A, Wohlschlegel J, Sturm N, Campbell D. Trypanosoma brucei spliced leader RNA maturation by the cap 1 2'-O-ribose methyltransferase and SLA1 H/ACA snoRNA pseudouridine synthase complex. Mol Cell Biol. 2009;29:1202-11 pubmed publisher
    ..The TbMTr1 complex specializes the SLA1 H/ACA snoRNP for efficient processing of multiple modifications on the SL RNA substrate. ..
  19. Lewdorowicz M, Yoffe Y, Zuberek J, Jemielity J, Stepinski J, Kierzek R, et al. Chemical synthesis and binding activity of the trypanosomatid cap-4 structure. RNA. 2004;10:1469-78 pubmed
    ..The spliced leader RNA (SL RNA) is joined to the 5' end of all mRNAs, thus donating a 5' cap that is characterized by complex ..
  20. Podlipaev S, Sturm N, Fiala I, Fernandes O, Westenberger S, Dollet M, et al. Diversity of insect trypanosomatids assessed from the spliced leader RNA and 5S rRNA genes and intergenic regions. J Eukaryot Microbiol. 2004;51:283-90 pubmed
    ..Our data revealed additional discrepancies between molecular phylogenetic data and cell morphology, rendering current trypanosomatid taxonomy unreliable. ..
  21. Maslov D, Westenberger S, Xu X, Campbell D, Sturm N. Discovery and barcoding by analysis of spliced leader RNA gene sequences of new isolates of Trypanosomatidae from Heteroptera in Costa Rica and Ecuador. J Eukaryot Microbiol. 2007;54:57-65 pubmed
    ..in Heteroptera was sampled using a culture-independent approach based on amplification and sequencing of Spliced Leader RNA gene repeats from environmental samples...
  22. Lustig Y, Sheiner L, Vagima Y, Goldshmidt H, Das A, Bellofatto V, et al. Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei. EMBO Rep. 2007;8:408-13 pubmed
    ..SLS was also induced under pH stress and might function as a master regulator in trypanosomes. SLS is reminiscent of, but distinct from, the unfolded protein response and can potentially act as a new target for parasite eradication. ..
  23. Liang X, Haritan A, Uliel S, Michaeli S. trans and cis splicing in trypanosomatids: mechanism, factors, and regulation. Eukaryot Cell. 2003;2:830-40 pubmed
  24. Lanchy J, Rentz C, Ivanovitch J, Lodmell J. Elements located upstream and downstream of the major splice donor site influence the ability of HIV-2 leader RNA to dimerize in vitro. Biochemistry. 2003;42:2634-42 pubmed
  25. Zeiner G, Sturm N, Campbell D. Exportin 1 mediates nuclear export of the kinetoplastid spliced leader RNA. Eukaryot Cell. 2003;2:222-30 pubmed
    ..This study demonstrates spatial and mechanistic similarities between the posttranscriptional trafficking of the kinetoplastid protozoan SL RNA and the metazoan cis-spliceosomal small nuclear RNAs...
  26. Cribb P, Serra E. One- and two-hybrid analysis of the interactions between components of the Trypanosoma cruzi spliced leader RNA gene promoter binding complex. Int J Parasitol. 2009;39:525-32 pubmed publisher
  27. Zamudio J, Mittra B, Campbell D, Sturm N. Hypermethylated cap 4 maximizes Trypanosoma brucei translation. Mol Microbiol. 2009;72:1100-10 pubmed
    ..A minimal level of mRNA cap ribose methylation is essential for trypanosome viability, providing the first functional role for the cap 4. ..
  28. Goldshmidt H, Matas D, Kabi A, Carmi S, Hope R, Michaeli S. Persistent ER stress induces the spliced leader RNA silencing pathway (SLS), leading to programmed cell death in Trypanosoma brucei. PLoS Pathog. 2010;6:e1000731 pubmed publisher
    ..However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS) pathway...
  29. Lee J, Cai G, Panigrahi A, Dunham Ems S, Nguyen T, Radolf J, et al. A TFIIH-associated mediator head is a basal factor of small nuclear spliced leader RNA gene transcription in early-diverged trypanosomes. Mol Cell Biol. 2010;30:5502-13 pubmed publisher
  30. Palenchar J, Liu W, Palenchar P, Bellofatto V. A divergent transcription factor TFIIB in trypanosomes is required for RNA polymerase II-dependent spliced leader RNA transcription and cell viability. Eukaryot Cell. 2006;5:293-300 pubmed
    ..The information gleaned from TbTFIIB studies furthers our understanding of SL RNA gene transcription and the elusive overall transcriptional processes in trypanosomes. ..
  31. Vandenberghe A, Meedel T, Hastings K. mRNA 5'-leader trans-splicing in the chordates. Genes Dev. 2001;15:294-303 pubmed
    ..SL trans-splicing is not known to occur in the vertebrates. However, because ascidians are primitive chordates related to vertebrate ancestors, our findings raise the possibility of ancestral SL trans-splicing in the vertebrate lineage. ..
  32. Santana D, Lukes J, Sturm N, Campbell D. Two sequence classes of kinetoplastid 5S ribosomal RNA gene revealed among bodonid spliced leader RNA gene arrays. FEMS Microbiol Lett. 2001;204:233-7 pubmed
    The spliced leader RNA genes of Bodo saltans, Cryptobia helicis and Dimastigella trypaniformis were analyzed as molecular markers for additional taxa within the suborder Bodonina...
  33. Fernandez C, Gregory W, Loke P, Maizels R. Full-length-enriched cDNA libraries from Echinococcus granulosus contain separate populations of oligo-capped and trans-spliced transcripts and a high level of predicted signal peptide sequences. Mol Biochem Parasitol. 2002;122:171-80 pubmed
    ..The oligo-capped and SL strategies represent efficient and complementary pathways to isolate full-length cDNA clones from this cestode parasite and, possibly, from related parasitic flatworms. ..
  34. Yu M, Orlando T, Sturm N, Zhou L, Saito R, Floeter Winter L, et al. Two distinct functional spliced leader RNA gene arrays in Leishmania tarentolae are found in several lizard Leishmania species. Int J Parasitol. 2002;32:1411-22 pubmed
    A second distinct array of spliced leader RNA genes has been found in several Leishmania species particular to lizards. This is the first report of two non-allelic arrays of spliced leader RNA genes within a species cell line...
  35. Lee K, Sommer R. Operon structure and trans-splicing in the nematode Pristionchus pacificus. Mol Biol Evol. 2003;20:2097-103 pubmed
    ..pacificus contains operons and that downstream genes are trans-spliced to SL2. Surprisingly, the one operon analyzed so far in P. pacificus is not conserved in C. elegans, suggesting unexpected genomic plasticity. ..
  36. Campbell D, Thomas S, Sturm N. Transcription in kinetoplastid protozoa: why be normal?. Microbes Infect. 2003;5:1231-40 pubmed
    ..Here, we present a broad overview of what is known about transcription in the kinetoplastids and what has yet to be determined. ..
  37. Schimanski B, Laufer G, Gontcharova L, GUNZL A. The Trypanosoma brucei spliced leader RNA and rRNA gene promoters have interchangeable TbSNAP50-binding elements. Nucleic Acids Res. 2004;32:700-9 pubmed
    ..brucei counterpart are homologous to SNAP50, a component of the human small nuclear RNA gene activation protein complex (SNAPc), both SLRNA and RRNA transcription in T.brucei may depend on a SNAPc-like transcription factor. ..
  38. Schimanski B, Brandenburg J, Nguyen T, Caimano M, GUNZL A. A TFIIB-like protein is indispensable for spliced leader RNA gene transcription in Trypanosoma brucei. Nucleic Acids Res. 2006;34:1676-84 pubmed
    ..for RNA polymerase II-mediated transcription of SLRNA genes, which encode the trans splicing-specific spliced leader RNA, suggests that trypanosomatids assemble a highly divergent set of these factors at the SLRNA promoter...
  39. Foldynova Trantirkova S, Paris Z, Sturm N, Campbell D, Lukes J. The Trypanosoma brucei La protein is a candidate poly(U) shield that impacts spliced leader RNA maturation and tRNA intron removal. Int J Parasitol. 2005;35:359-66 pubmed
    ..As the universal substrate for trans-splicing, the spliced leader RNA is transcribed as a precursor with just such a tail...
  40. Ruan J, Arhin G, Ullu E, Tschudi C. Functional characterization of a Trypanosoma brucei TATA-binding protein-related factor points to a universal regulator of transcription in trypanosomes. Mol Cell Biol. 2004;24:9610-8 pubmed
    ..showed that TRF4 is recruited to the Pol I-transcribed procyclic acidic repetitive genes, Pol II-transcribed spliced leader RNA genes, and Pol III-transcribed U-snRNA and 7SL RNA genes, thus supporting a role for TbTRF4 in transcription ..
  41. Lee J, Nguyen T, Schimanski B, GUNZL A. Spliced leader RNA gene transcription in Trypanosoma brucei requires transcription factor TFIIH. Eukaryot Cell. 2007;6:641-9 pubmed
    ..Since we also identified orthologues of the TFIIH subunits XPB, p52/TFB2, and p44/SSL1 copurifying with TbXPD, we concluded that the parasite harbors a TFIIH which is indispensable for SL RNA gene transcription. ..
  42. Shaked H, Wachtel C, Tulinski P, Yahia N, Barda O, Darzynkiewicz E, et al. Establishment of an in vitro trans-splicing system in Trypanosoma brucei that requires endogenous spliced leader RNA. Nucleic Acids Res. 2010;38:e114 pubmed publisher
    ..This study is the first step towards further elucidating the mechanism of trans-splicing, an essential reaction which determines the trypanosome transcriptome. ..
  43. Gilinger G, Bellofatto V. Trypanosome spliced leader RNA genes contain the first identified RNA polymerase II gene promoter in these organisms. Nucleic Acids Res. 2001;29:1556-64 pubmed
    ..We show here that the in vitro transcription extract contains a binding activity that is specific for the initiator element and thus may participate in recruiting RNA polymerase II to the SL RNA gene promoter. ..
  44. Blumenthal T, Evans D, Link C, Guffanti A, Lawson D, Thierry Mieg J, et al. A global analysis of Caenorhabditis elegans operons. Nature. 2002;417:851-4 pubmed
    ..elegans genes. Numerous examples of co-transcription of genes encoding functionally related proteins are evident. Inspection of the operon list should reveal previously unknown functional relationships. ..
  45. Huthoff H, Berkhout B. Multiple secondary structure rearrangements during HIV-1 RNA dimerization. Biochemistry. 2002;41:10439-45 pubmed
    ..The folding properties of the wild-type RNA and the defects caused by the mutations can be fully understood in terms of the free energy changes associated with secondary structure rearrangements. ..
  46. Mittra B, Zamudio J, Bujnicki J, Stepinski J, Darzynkiewicz E, Campbell D, et al. The TbMTr1 spliced leader RNA cap 1 2'-O-ribose methyltransferase from Trypanosoma brucei acts with substrate specificity. J Biol Chem. 2008;283:3161-72 pubmed
    ..With similarities to human cap 1 methyltransferase activity, TbMTr1 is an excellent model for higher eukaryotic cap 1 methyltransferases and the consequences of cap 1 modification. ..
  47. Mandelboim M, Barth S, Biton M, Liang X, Michaeli S. Silencing of Sm proteins in Trypanosoma brucei by RNA interference captured a novel cytoplasmic intermediate in spliced leader RNA biogenesis. J Biol Chem. 2003;278:51469-78 pubmed
    ..The SL RNA biogenesis pathway differs from that of U sn ribonucleoproteins (RNPs) in that it is the only RNA that binds Sm proteins that were stabilized under Sm depletion in a novel RNP, which we termed SL RNP-C. ..
  48. Zhang H, Hou Y, Miranda L, Campbell D, Sturm N, Gaasterland T, et al. Spliced leader RNA trans-splicing in dinoflagellates. Proc Natl Acad Sci U S A. 2007;104:4618-23 pubmed
    ..AF 512889, DQ 864761-DQ 864971, DQ 867053-DQ 867070, DQ 884413-DQ 884451, EF 133854-EF 133905, EF 133961-EF 134003, EF 134083-EF 134402, EF 141835, and EF 143070-EF 143105). ..
  49. Spiliotis M, Brehm K. Echinococcus multilocularis: identification and molecular characterization of a Ral-like small GTP-binding protein. Exp Parasitol. 2004;107:163-72 pubmed
    ..The data presented herein provide a solid basis for further investigations on Ras-Ral signaling mechanisms in Echinococcus. ..
  50. Das A, Li H, Liu T, Bellofatto V. Biochemical characterization of Trypanosoma brucei RNA polymerase II. Mol Biochem Parasitol. 2006;150:201-10 pubmed
    ..brucei RNA polymerase II. While both bioinformatics and biochemical analysis have focused on the subunit structure of trypanosome RNA polymerases, this is the first study that reveals a functional RNA polymerase II enzyme. ..
  51. Brehm K, Wolf M, Beland H, Kroner A, Frosch M. Analysis of differential gene expression in Echinococcus multilocularis larval stages by means of spliced leader differential display. Int J Parasitol. 2003;33:1145-59 pubmed
  52. Graber J, Salisbury J, Hutchins L, Blumenthal T. C. elegans sequences that control trans-splicing and operon pre-mRNA processing. RNA. 2007;13:1409-26 pubmed
    ..in Caenorhabditis elegans are generated through a trans-splicing reaction that adds one of two classes of spliced leader RNA to an independently transcribed pre-mRNA...
  53. Derelle R, Momose T, Manuel M, Da Silva C, Wincker P, Houliston E. Convergent origins and rapid evolution of spliced leader trans-splicing in metazoa: insights from the ctenophora and hydrozoa. RNA. 2010;16:696-707 pubmed publisher