RNA editing in trypanosomes

Guide RNAs are encoded in maxicircle and minicircle DNA of trypanosome mitochondria. They play a pivotal role in RNA editing, a process during which the nucleotide sequence of mitochondrial RNAs is altered by U-insertion and deletion. Guide RNAs vary in length from 35 to 78 nucleotides, which correlates with the variation in length of the three functionally important regions of which they are composed: (i) a 4–14 nucleotide ‘anchor’ sequence embedded in the 5′ region, which is complementary to a target sequence on the pre-edited RNA downstream of an editing domain, (ii) a middle part containing the editing information, which ranges from guiding the insertion of just one U into one site to that of the insertion of 32 Us into 10 sites, and (iii) a 5–24 nucleotide 3′ terminal oligo [U] extension. Moreover, a variable uridylation site creates gRNAs containing a varying segment of editing information for the same domain. Comparison of different guide RNAs demonstrates that, besides the U-tail, they have no obvious common primary and secondary sequence motifs, each particular sequence being unique. The occurrence in vivo and the synthesis in vitro of chimeric molecules, in which a guide RNA is covalently linked through its 3′ U-tail to an editing site of a pre-edited RNA, suggests that RNA editing occurs by consecutive transesterification reactions and is evidence that the guide RNAs not only provide the genetic information, but also the Us themselves.

[1]  H. van Steeg,et al.  RNA editing in transcripts of the mitochondrial genes of the insect trypanosome Crithidia fasciculata. , 1990, The EMBO journal.

[2]  Kenneth Stuart,et al.  Extensive editing of the cytochrome c oxidase III transcript in Trypanosoma brucei , 1988, Cell.

[3]  B. Sollner-Webb,et al.  RNA editing involves indiscriminate U changes throughout precisely defined editing domains , 1990, Cell.

[4]  M. Ouellette,et al.  Targeted insertion of the neomycin phosphotransferase gene into the tubulin gene cluster of Trypanosoma brucei , 1990, Nature.

[5]  R. Benne,et al.  Conserved genes encode guide RNAs in mitochondria of Crithidia fasciculata. , 1991, The EMBO journal.

[6]  Larry Simpson,et al.  Kinetoplast DNA minicircles encode guide RNAs for editing of cytochrome oxidase subunit III mRNA , 1990, Cell.

[7]  K. Stuart,et al.  An extensively edited mitochondrial transcript in kinetoplastids encodes a protein homologous to ATPase subunit 6 , 1990, Cell.

[8]  S. Hajduk,et al.  The molecular biology of trypanosomes. , 1982, Annual review of biochemistry.

[9]  K. Stuart,et al.  The MURF3 gene of T. brucei contains multiple domains of extensive editing and is homologous to a subunit of NADH dehydrogenase , 1990, Cell.

[10]  P. Hagerman,et al.  Sequence-directed curvature of DNA. , 1986, Nature.

[11]  L. Simpson,et al.  Chimeric gRNA-mRNA molecules with oligo(U) tails covalently linked at sites of RNA editing suggest that U addition occurs by transesterification , 1991, Cell.

[12]  K. Stuart.  RNA editing in mitochondrial mRNA of trypanosomatids. , 1991, Trends in biochemical sciences.

[13]  S. Hajduk,et al.  Kinetoplastid RNA editing: In vitro formation of cytochrome b gRNA-mRNA chimeras from synthetic substrate RNAs , 1992, Cell.

[14]  L. Simpson,et al.  Kinetoplast DNA in trypanosomid flagellates. , 1986, International review of cytology.

[15]  L. Simpson,et al.  Guide RNAs in kinetoplastid mitochondria have a nonencoded 3′ oligo(U) tail involved in recognition of the preedited region , 1990, Cell.

[16]  L. Simpson,et al.  The Leishmania kinetoplast-mitochondrion contains terminal uridylyltransferase and RNA ligase activities. , 1989, The Journal of biological chemistry.

[17]  T. Cech,et al.  RNA editing: World's smallest introns? , 1991, Cell.

[18]  J. Shaw,et al.  RNA editing and the mitochondrial cryptogenes of kinetoplastid protozoa , 1989, Cell.

[19]  K. Stuart,et al.  Guide RNAs for transcripts with developmentally regulated RNA editing are present in both life cycle stages of Trypanosoma brucei , 1992, Molecular and cellular biology.

[20]  S. Hajduk,et al.  Addition of uridines to edited RNAs in trypanosome mitochondria occurs independently of transcription. , 1990, The Journal of biological chemistry.

[21]  M. Steinert,et al.  Sequence heterogeneity in kinetoplast DNA: reassociation kinetics. , 1980, Plasmid.

[22]  P. Myler,et al.  Maxicircle CR1 transcripts of Trypanosoma brucei are edited and developmentally regulated and encode a putative iron-sulfur protein homologous to an NADH dehydrogenase subunit , 1992, Molecular and cellular biology.

[23]  G. Nossal,et al.  The molecular and cellular basis of affinity maturation in the antibody response , 1992, Cell.

[24]  S. Hajduk,et al.  Organization of minicircle genes for guide RNAs in trypanosoma brucei , 1990, Cell.

[25]  P. Myler,et al.  Extensive editing of both processed and preprocessed maxicircle CR6 transcripts in Trypanosoma brucei. , 1992, The Journal of biological chemistry.

[26]  L. Simpson,et al.  Leishmania tarentolae minicircles of different sequence classes encode single guide RNAs located in the variable region approximately 150 bp from the conserved region. , 1991, Nucleic acids research.

[27]  K. Stuart,et al.  In vitro guide RNA/mRNA chimaera formation in Trypanosoma bruceiRNA editing , 1992, Nature.

[28]  P. Perlman,et al.  The unusual varl gene of yeast mitochondrial DNA. , 1985, Science.

[29]  J. Burke,et al.  Intron within the large rRNA gene of N. crassa mitochondria: A long open reading frame and a consensus sequence possibly important in splicing , 1982, Cell.

[30]  R. Benne,et al.  Evolution of the mitochondrial protein synthetic machinery. , 1987, Bio Systems.

[31]  R. Benne.  Mitochondrial genes in trypanosomes , 1985 .

[32]  G. Cross,et al.  Expression of a bacterial gene in a trypanosomatid protozoan. , 1989, Science.

[33]  R. Benne,et al.  Transcripts from the frameshifted MURF3 gene from Crithidia fasciculata are edited by U insertion at multiple sites. , 1988, The EMBO journal.

[34]  Larry Simpson,et al.  A model for RNA editing in kinetoplastid mitochondria: RNA molecules transcribed from maxicircle DNA provide the edited information , 1990, Cell.

[35]  L. Simpson,et al.  The mitochondrial genome of kinetoplastid protozoa: genomic organization, transcription, replication, and evolution. , 1987, Annual review of microbiology.

[36]  A. Frasch,et al.  The kinetoplast DNA of Trypanosoma equiperdum. , 1980, Biochimica et biophysica acta.

[37]  G. Buck,et al.  In vitro 3' end processing and poly(A) tailing of RNA in Trypanosoma cruzi. , 1989, Nucleic acids research.

[38]  D. Vanhecke,et al.  Kinetoplast minicircle DNA of Trypanosoma evansi encode guide RNA genes. , 1992, Nucleic acids research.

[39]  L. Simpson,et al.  Specific cleavage of kinetoplast minicircle DNA from Leishmania tarentolae by mung bean nuclease and identification of several additional minicircle sequence classes , 1986, Nucleic Acids Res..

[40]  S. Hajduk,et al.  Trypanosoma equiperdum minicircles encode three distinct primary transcripts which exhibit guide RNA characteristics , 1991, Molecular and cellular biology.

[41]  R. Benne,et al.  Major transcript of the frameshifted coxll gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA , 1986, Cell.

[42]  R. Benne.  RNA editing in trypanosomes: is there a message? , 1990, Trends in genetics : TIG.

[43]  L. Simpson,et al.  Partially edited mRNAs for cytochrome b and subunit III of cytochrome oxidase from leishmania tarentolae mitochondria: RNA editing intermediates , 1990, Cell.