guide rna


Summary: Small kinetoplastid mitochondrial RNA that plays a major role in RNA EDITING. These molecules form perfect hybrids with edited mRNA sequences and possess nucleotide sequences at their 5'-ends that are complementary to the sequences of the mRNA's immediately downstream of the pre-edited regions.

Top Publications

  1. Li L, Ye K. Crystal structure of an H/ACA box ribonucleoprotein particle. Nature. 2006;443:302-7 pubmed
  2. Kiss A, Jady B, Bertrand E, Kiss T. Human box H/ACA pseudouridylation guide RNA machinery. Mol Cell Biol. 2004;24:5797-807 pubmed
  3. Pai R, Oppegard L, Connell G. Sequence and structural requirements for optimal guide RNA-directed insertional editing within Leishmania tarentolae. RNA. 2003;9:469-83 pubmed
    The coding sequence of several mitochondrial mRNAs of the trypanosomatid family of protozoa is created by the guide RNA-directed insertion and deletion of uridylates (Us)...
  4. King T, Liu B, McCully R, Fournier M. Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center. Mol Cell. 2003;11:425-35 pubmed
    ..The possibility that modifying snoRNPs might affect ribosome structure in other ways is also discussed. ..
  5. Aittaleb M, Rashid R, Chen Q, Palmer J, Daniels C, Li H. Structure and function of archaeal box C/D sRNP core proteins. Nat Struct Biol. 2003;10:256-63 pubmed publisher
    ..A model of box C/D snoRNP assembly is proposed based on the presented structural and biochemical data...
  6. Bachellerie J, Cavaille J, Huttenhofer A. The expanding snoRNA world. Biochimie. 2002;84:775-90 pubmed
    ..termed box C/D and H/ACA snoRNAs, respectively, and exert their function through the formation of a canonical guide RNA duplex at the modification site...
  7. Zhou T, Kim J, Kilani A, Kim K, Dunn W, Jo S, et al. In vitro selection of external guide sequences for directing RNase P-mediated inhibition of viral gene expression. J Biol Chem. 2002;277:30112-20 pubmed
    ..These results also demonstrate the potential for using the selection procedure as a general approach for the generation of highly effective EGSs for gene-targeting application. ..
  8. Ofengand J. Ribosomal RNA pseudouridines and pseudouridine synthases. FEBS Lett. 2002;514:17-25 pubmed
    ..In eukaryotes, and probably also in archaea, selection and modification is done by a guide RNA-protein complex. No unique specific role for ribosomal pseudouridines has been identified...
  9. Speckmann W, Li Z, Lowe T, Eddy S, Terns R, Terns M. Archaeal guide RNAs function in rRNA modification in the eukaryotic nucleus. Curr Biol. 2002;12:199-203 pubmed
    ..Our studies have revealed the remarkable ability of archaeal Box C/D RNAs to assemble into functional RNA-protein complexes in the eukaryotic nucleus. ..

Scientific Experts

More Information


  1. MULLER U, Göringer H. Mechanism of the gBP21-mediated RNA/RNA annealing reaction: matchmaking and charge reduction. Nucleic Acids Res. 2002;30:447-55 pubmed
    The guide RNA-binding protein gBP21 has been characterized as a mitochondrial RNA/RNA annealing factor...
  2. Nolivos S, Carpousis A, Clouet d Orval B. The K-loop, a general feature of the Pyrococcus C/D guide RNAs, is an RNA structural motif related to the K-turn. Nucleic Acids Res. 2005;33:6507-14 pubmed
    ..For the C/D guides with a 3 nt-spacer we show that the sequence and length is also important. The K-loop could improve the stability of the C/D guide RNAs in Pyrococcal species, which are extreme hyperthermophiles...
  3. Golden D, Hajduk S. The importance of RNA structure in RNA editing and a potential proofreading mechanism for correct guide RNA:pre-mRNA binary complex formation. J Mol Biol. 2006;359:585-96 pubmed
    ..The mechanism relies on the thermodynamic stability supplied to the RNA complex through Watson-Crick base-pairing. Through mutations in the gRNA, we demonstrate the importance of gRNA structure to the RNA editing reaction. ..
  4. Bernstein E, Caudy A, Hammond S, Hannon G. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363-6 pubmed
    ..The enzyme has a distinctive structure, which includes a helicase domain and dual RNase III motifs. Dicer also contains a region of homology to the RDE1/QDE2/ARGONAUTE family that has been genetically linked to RNAi. ..
  5. Kiss T, Fayet E, Jády B, Richard P, Weber M. Biogenesis and intranuclear trafficking of human box C/D and H/ACA RNPs. Cold Spring Harb Symp Quant Biol. 2006;71:407-17 pubmed
    ..This suggests that a cell-cycle-dependent, dynamic localization of hTR to telomeres may play an important regulatory role in human telomere synthesis...
  6. Hernandez A, Panigrahi A, Cifuentes Rojas C, Sacharidou A, Stuart K, Cruz Reyes J. Determinants for association and guide RNA-directed endonuclease cleavage by purified RNA editing complexes from Trypanosoma brucei. J Mol Biol. 2008;381:35-48 pubmed publisher
    ..editing complexes recognize many pre-edited mRNA sites and modify them via cycles of three catalytic steps: guide RNA (gRNA)-directed cleavage, insertion or deletion of uridylates at the 3'-terminus of the upstream cleaved piece, ..
  7. Cifuentes Rojas C, Pavia P, Hernandez A, Osterwisch D, Puerta C, Cruz Reyes J. Substrate determinants for RNA editing and editing complex interactions at a site for full-round U insertion. J Biol Chem. 2007;282:4265-76 pubmed
    ..Importantly, most observed cross-linking interactions are both conserved and relatively stable at ES2 and ES1 in hybrid substrates. However, they were also detected as transient low-stability contacts in a non-edited transcript. ..
  8. Ye K. H/ACA guide RNAs, proteins and complexes. Curr Opin Struct Biol. 2007;17:287-92 pubmed
    ..The binding of guide RNA is directed by its conserved secondary structure and sequence motifs, which enables guide RNA with different ..
  9. Reifur L, Yu L, Cruz Reyes J, Vanhartesvelt M, Koslowsky D. The impact of mRNA structure on guide RNA targeting in kinetoplastid RNA editing. PLoS ONE. 2010;5:e12235 pubmed publisher
    Mitochondrial mRNA editing in Trypanosoma brucei requires the specific interaction of a guide RNA with its cognate mRNA...
  10. Schattner P, Decatur W, Davis C, Ares M, Fournier M, Lowe T. Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome. Nucleic Acids Res. 2004;32:4281-96 pubmed
    ..One of the largest families of small RNAs in eukaryotes is the H/ACA small nucleolar RNAs (snoRNAs), most of which guide RNA pseudouridine formation...
  11. Frank F, Sonenberg N, Nagar B. Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2. Nature. 2010;465:818-22 pubmed publisher
    ..6 mM) or GMP (3.3 mM). This study provides structural evidence for nucleotide-specific interactions in the MID domain of eukaryotic AGO proteins and explains the observed preference for U or A at the 5' end of miRNAs. ..
  12. Weng J, Aphasizheva I, Etheridge R, Huang L, Wang X, Falick A, et al. Guide RNA-binding complex from mitochondria of trypanosomatids. Mol Cell. 2008;32:198-209 pubmed publisher
    ..Throughout the processes of pre-mRNA polyadenylation, guide RNA (gRNA) uridylylation and annealing to mRNA, and editing reactions, several multiprotein complexes must engage in ..
  13. Reifur L, Koslowsky D. Trypanosoma brucei ATPase subunit 6 mRNA bound to gA6-14 forms a conserved three-helical structure. RNA. 2008;14:2195-211 pubmed publisher
    ..These results lead us to conclude that at least two mRNA/gRNA pairs with distinct editing sites and distinct primary sequences fold to a three-helical secondary configuration that persists through the first few editing events. ..
  14. Stuart K, Schnaufer A, Ernst N, Panigrahi A. Complex management: RNA editing in trypanosomes. Trends Biochem Sci. 2005;30:97-105 pubmed
    ..The dynamic processes, which might entail interactions among multiprotein complexes and changes in their composition and conformation, remain to be elucidated. ..
  15. Ammerman M, Fisk J, Read L. gRNA/pre-mRNA annealing and RNA chaperone activities of RBP16. RNA. 2008;14:1069-80 pubmed publisher
    ..Our data suggest that the mechanism by which RBP16 facilitates RNA editing involves its capacity to modulate RNA secondary structure and promote gRNA/pre-mRNA annealing. ..
  16. Parker J, Roe S, Barford D. Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature. 2005;434:663-6 pubmed publisher
    RNA interference and related RNA silencing phenomena use short antisense guide RNA molecules to repress the expression of target genes...
  17. Köberle C, Kaufmann S, Patzel V. Selecting effective siRNAs based on guide RNA structure. Nat Protoc. 2006;1:1832-9 pubmed
    ..Although this procedure is new and remains to be validated by the community, it allows reliable identification of highly active siRNAs that can be used for functional target validation or drug development. ..
  18. Goulah C, Read L. Differential effects of arginine methylation on RBP16 mRNA binding, guide RNA (gRNA) binding, and gRNA-containing ribonucleoprotein complex (gRNP) formation. J Biol Chem. 2007;282:7181-90 pubmed
    ..stable complexes: a 5 S multiprotein complex and an 11 S complex consisting of the 5 S complex associated with guide RNA (gRNA)...
  19. Nakashima A, Takaku H, Shibata H, Negishi Y, Takagi M, Tamura M, et al. Gene silencing by the tRNA maturase tRNase ZL under the direction of small-guide RNA. Gene Ther. 2007;14:78-85 pubmed
    ..specific mRNA by the long form of tRNA 3'-processing endoribonuclease (tRNase Z(L)) under the direction of small-guide RNA (sgRNA)...
  20. Tamura M, Nashimoto C, Miyake N, Daikuhara Y, Ochi K, Nashimoto M. Intracellular mRNA cleavage by 3' tRNase under the direction of 2'-O-methyl RNA heptamers. Nucleic Acids Res. 2003;31:4354-60 pubmed
    ..tRNA 3' processing endoribonuclease (3'-tRNase) can cleave any RNA at any site under the direction of small guide RNA (sgRNA) in vitro...
  21. Ochsenreiter T, Hajduk S. Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria generates protein diversity. EMBO Rep. 2006;7:1128-33 pubmed
    ..We show that COXIII mRNA can be alternatively edited by a mechanism using an alternative guide RNA to make a stable mRNA...
  22. Ochsenreiter T, Cipriano M, Hajduk S. KISS: the kinetoplastid RNA editing sequence search tool. RNA. 2007;13:1-4 pubmed
    ..Using an online format, KISS 1.0 allows the mapping and visualization of all known T. brucei gRNAs to minicircle genes and to potential mRNA substrates for RNA editing. ..
  23. M ller U, Lambert L, G ringer H. Annealing of RNA editing substrates facilitated by guide RNA-binding protein gBP21. EMBO J. 2001;20:1394-404 pubmed publisher
    ..The data suggest a factor-like contribution of gBP21 to the RNA editing process by accelerating the rate of gRNA-pre-mRNA anchor formation...
  24. Maslov D, Simpson L. The polarity of editing within a multiple gRNA-mediated domain is due to formation of anchors for upstream gRNAs by downstream editing. Cell. 1992;70:459-67 pubmed
    ..We suggest that a role of G-U base pairs is to allow breathing of the edited mRNA-gRNA hybrid and formation of the upstream anchor hybrid...
  25. Hayman M, Read L. Trypanosoma brucei RBP16 is a mitochondrial Y-box family protein with guide RNA binding activity. J Biol Chem. 1999;274:12067-74 pubmed
    ..The arginine and glycine rich C terminus in combination with the cold shock domain predicts that RBP16 will be involved in the regulation of gene expression at the posttranscriptional level...
  26. Jády B, Kiss T. A small nucleolar guide RNA functions both in 2'-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA. EMBO J. 2001;20:541-51 pubmed
    ..The U85 is the first example of a snoRNA that directs modification of an RNA polymerase II-transcribed spliceosomal RNA and that functions both in RNA pseudouridylation and 2'-O-methylation. ..
  27. McManus M, Shimamura M, Grams J, Hajduk S. Identification of candidate mitochondrial RNA editing ligases from Trypanosoma brucei. RNA. 2001;7:167-75 pubmed
    ..These findings provide strong support for the enzymatic cascade model for kinetoplastid RNA editing...
  28. Maslov D, Sturm N, Niner B, Gruszynski E, Peris M, Simpson L. An intergenic G-rich region in Leishmania tarentolae kinetoplast maxicircle DNA is a pan-edited cryptogene encoding ribosomal protein S12. Mol Cell Biol. 1992;12:56-67 pubmed
    ..A minicircle-encoded gRNA overlaps 12 editing sites in G6 mRNA, and chimeric gRNA/mRNA molecules were shown to exist, in agreement with the transesterification model for editing...
  29. Kabb A, Oppegard L, McKenzie B, Connell G. A mRNA determinant of gRNA-directed kinetoplastid editing. Nucleic Acids Res. 2001;29:2575-80 pubmed
    ..We demonstrate here that gRNA binding alone is insufficient to create an editing site and that the mRNA sequence near an editing site is an additional determinant affecting the efficiency of the reaction. ..
  30. Fatica A, Tollervey D. Insights into the structure and function of a guide RNP. Nat Struct Biol. 2003;10:237-9 pubmed
  31. Kraus G, Geffin R, Spruill G, Young A, Seivright R, Cardona D, et al. Cross-clade inhibition of HIV-1 replication and cytopathology by using RNase P-associated external guide sequences. Proc Natl Acad Sci U S A. 2002;99:3406-11 pubmed
    ..Viral replication and cytopathology associated with infection of multiple HIV-1 clades can be effectively inhibited in CD4(+) cells expressing the RNase P-associated U5 EGS (560) molecule. ..
  32. Savill N, Higgs P. Redundant and non-functional guide RNA genes in Trypanosoma brucei are a consequence of multiple genes per minicircle. Gene. 2000;256:245-52 pubmed
    ..We also analyse the available minicircle sequence data and conclude that T. brucei is at a transient stage in this process. In addition, ten new putative gRNAs have been discovered. ..
  33. Ernst N, Panicucci B, Igo R, Panigrahi A, Salavati R, Stuart K. TbMP57 is a 3' terminal uridylyl transferase (TUTase) of the Trypanosoma brucei editosome. Mol Cell. 2003;11:1525-36 pubmed
    ..the addition of primarily a single U to single-stranded (ss) RNA and adds the number of Us specified by a guide RNA to insertion editing-like substrates...
  34. Kala S, Salavati R. OB-fold domain of KREPA4 mediates high-affinity interaction with guide RNA and possesses annealing activity. RNA. 2010;16:1951-67 pubmed publisher
    KREPA4, also called MP24, is an essential mitochondrial guide RNA (gRNA)-binding protein with a preference for the 3' oligo(U) tail in trypanosomes...
  35. Blum B, Bakalara N, Simpson L. A model for RNA editing in kinetoplastid mitochondria: "guide" RNA molecules transcribed from maxicircle DNA provide the edited information. Cell. 1990;60:189-98 pubmed
  36. K ller J, M ller U, Schmid B, Missel A, Kruft V, Stuart K, et al. Trypanosoma brucei gBP21. An arginine-rich mitochondrial protein that binds to guide RNA with high affinity. J Biol Chem. 1997;272:3749-57 pubmed
    ..The protein was named gBP21 for guide RNA-binding protein of 21 kDa...
  37. Maslov D, Hollar L, Haghighat P, Nawathean P. Demonstration of mRNA editing and localization of guide RNA genes in kinetoplast-mitochondria of the plant trypanosomatid Phytomonas serpens. Mol Biochem Parasitol. 1998;93:225-36 pubmed
    ..A gRNA gene for the second block of RPSl2 was found on a minicircle sequenced previously. On each minicircle, a gRNA gene is located in the variable region in a similar position and orientation with respect to the conserved regions. ..
  38. Ma M, Benimetskaya L, Lebedeva I, Dignam J, Takle G, Stein C. Intracellular mRNA cleavage induced through activation of RNase P by nuclease-resistant external guide sequences. Nat Biotechnol. 2000;18:58-61 pubmed
    ..Furthermore, the downregulation is dependent on the presence of, and base sequence in, the T-loop. Similar observations were made with an EGS targeted to the bcl-xL mRNA. ..
  39. Ochsenreiter T, Cipriano M, Hajduk S. Alternative mRNA editing in trypanosomes is extensive and may contribute to mitochondrial protein diversity. PLoS ONE. 2008;3:e1566 pubmed publisher
    ..These findings show that alternative editing of mitochondrial mRNAs is common in T. brucei and expands the diversity of mitochondrial proteins in these organisms. ..
  40. Alatortsev V, Cruz Reyes J, Zhelonkina A, Sollner Webb B. Trypanosoma brucei RNA editing: coupled cycles of U deletion reveal processive activity of the editing complex. Mol Cell Biol. 2008;28:2437-45 pubmed publisher
    ..brucei mRNAs edited in vivo. This unexpected editing is most likely due to alternate mRNA:guide RNA (gRNA) alignment forming a hyphenated anchor; its having only a 2-bp proximal duplex helps explain the ..
  41. Baker D, Seyfried N, Li H, Orlando R, Terns R, Terns M. Determination of protein-RNA interaction sites in the Cbf5-H/ACA guide RNA complex by mass spectrometric protein footprinting. Biochemistry. 2008;47:1500-10 pubmed publisher
    ..archaea, these modifications are carried out by H/ACA ribonucleoprotein (RNP) complexes, composed of an H/ACA guide RNA and four proteins, including the pseudouridine synthase, Cbf5...
  42. Omer A, Lowe T, Russell A, Ebhardt H, Eddy S, Dennis P. Homologs of small nucleolar RNAs in Archaea. Science. 2000;288:517-22 pubmed
    ..snoRNA-based rRNA processing was therefore probably present in the last common ancestor of Archaea and Eukarya, predating the evolution of a morphologically distinct nucleolus...
  43. Ma J, Yuan Y, Meister G, Pei Y, Tuschl T, Patel D. Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature. 2005;434:666-70 pubmed publisher
    ..mechanism mediated by the RNA-induced silencing complex (RISC), which is composed of a single-stranded guide RNA and an Argonaute protein...
  44. Cruz Reyes J, Zhelonkina A, Rusche L, Sollner Webb B. Trypanosome RNA editing: simple guide RNA features enhance U deletion 100-fold. Mol Cell Biol. 2001;21:884-92 pubmed
    ..Our data also have implications about evolutionary forces active in RNA editing. ..
  45. Barnor J, Endo Y, Habu Y, Miyano Kurosaki N, Kitano M, Yamamoto H, et al. Effective inhibition of HIV-1 replication in cultured cells by external guide sequences and ribonuclease P. Bioorg Med Chem Lett. 2004;14:4941-4 pubmed
    ..HIV-1 expression was inhibited by the tRNA(met)-EGS-U5 and U6-EGS-U5 from the tRNA(met) and U6 promoters, respectively. There was no difference in the inhibitory effects on HIV-1 expression between the tRNA(met) and U6 promoters. ..
  46. Tycowski K, Aab A, Steitz J. Guide RNAs with 5' caps and novel box C/D snoRNA-like domains for modification of snRNAs in metazoa. Curr Biol. 2004;14:1985-95 pubmed
    ..Each particle is composed of a short guide RNA and a set of several proteins...
  47. Kiss A, Jady B, Darzacq X, Verheggen C, Bertrand E, Kiss T. A Cajal body-specific pseudouridylation guide RNA is composed of two box H/ACA snoRNA-like domains. Nucleic Acids Res. 2002;30:4643-9 pubmed
    ..Here, we describe an unusual mammalian pseudouridylation guide RNA, called U93, that is composed of two tandemly arranged box H/ACA RNA domains...
  48. Blom D, Burg Jv -, Breek C, Speijer D, Muijsers A, Benne R. Cloning and characterization of two guide RNA-binding proteins from mitochondria of Crithidia fasciculata: gBP27, a novel protein, and gBP29, the orthologue of Trypanosoma brucei gBP21. Nucleic Acids Res. 2001;29:2950-62 pubmed
    ..Together, these results suggest that the proteins are part of a large macromolecular complex(es). We infer that gBP29 and gBP27 are components of the C.fasciculata editing machinery that may interact with gRNAs...
  49. Schumacher M, Karamooz E, Zíková A, Trantirek L, Lukes J. Crystal structures of T. brucei MRP1/MRP2 guide-RNA binding complex reveal RNA matchmaking mechanism. Cell. 2006;126:701-11 pubmed
    ..Thus, MRP1/MRP2 acts as an RNA matchmaker by stabilizing the RNA molecule in an unfolded conformation suitable for RNA-RNA hybridization. ..
  50. Gao G, Kapushoc S, Simpson A, Thiemann O, Simpson L. Guide RNAs of the recently isolated LEM125 strain of Leishmania tarentolae: an unexpected complexity. RNA. 2001;7:1335-47 pubmed
    ..We propose a functional explanation for the existence of redundant gRNAs in this strain. ..
  51. Pelletier M, Xu Y, Wang X, Zahariev S, Pongor S, Aletta J, et al. Arginine methylation of a mitochondrial guide RNA binding protein from Trypanosoma brucei. Mol Biochem Parasitol. 2001;118:49-59 pubmed
    ..These results suggest that protein arginine methylation is a common posttranslational modification in trypanosomes, and that it may regulate the function of RBP16. ..
  52. Manival X, Charron C, Fourmann J, Godard F, Charpentier B, Branlant C. Crystal structure determination and site-directed mutagenesis of the Pyrococcus abyssi aCBF5-aNOP10 complex reveal crucial roles of the C-terminal domains of both proteins in H/ACA sRNP activity. Nucleic Acids Res. 2006;34:826-39 pubmed publisher
    ..By gel filtration assay, we showed that aNOP10 can dimerize in solution. As both residues Y41 and L48 were needed for dimerization, the dimerization likely takes place by interaction of parallel alpha-helices...
  53. Leung S, Koslowsky D. Interactions of mRNAs and gRNAs involved in trypanosome mitochondrial RNA editing: structure probing of an mRNA bound to its cognate gRNA. RNA. 2001;7:1803-16 pubmed
    ..In combination with our previous studies, these new data provide additional support for the predicted secondary structure of interacting gRNA/mRNA pairs. ..