Uridine insertion/deletion RNA editing in trypanosome mitochondria — a review

Estévez, Antonio M.; Simpson, Larry

doi:10.1016/s0378-1119(99)00437-0

Cited by 113 publications

(64 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The profile of ribonucleotides adjacent to deletion sites is unlike what is seen at insertion sites+ As a point of reference, the baseline percentage of ribonucleotides adjacent to deletion sites is lower because there are many fewer deletion sites than insertion sites in edited regions of RNA: 5+79% of ribonucleotides in edited regions are located adjacent to a deleted U+ The proportions of As, Gs, and Cs upstream of inserted Us vary less than at insertion sites, and are not significantly different from random (see Fig+ 3B)+ Us adjacent to deletion sites, consistent with the current mechanistic model of U deletion (Hajduk et al+, 1997;Stuart et al+, 1997;Estevez & Simpson, 1999), are considered to be downstream of deleted Us+ This is supported by studies of in vitro U deletion, which indicate that all Us 59 to the position of cleavage at the editing site are removed down to the first non-U ribonucleotide, and thus, that nondeleted Us are not upstream of deleted Us (CruzReyes & Solner-Webb, 1996; Seiwert et al+, 1996; Lawson et al+, 2000)+ The relatively high proportion of Cs upstream of deletion sites contrasts with the strong bias against C upstream of insertion sites+ The finding that Cs are well represented in this position at deletion sites is surprising+ This context was suggested to pose a particular difficulty because the complimentary G in the gRNA would be predicted to pair with the U to be deleted (Feagin, 1990;Sturm et al+, 1992)+ This was termed the "CU paradox" (Sturm et al+, 1992), and was suggested to possibly be a contributing factor to misediting at deletion sites+ However, the relatively favorable probability that a C in an edited region will be found in this context suggests that it is not selected against, and raises the pos- The same analysis performed for ribonucleotides upstream of deleted Us+ For this analysis, encoded Us are considered never to be upstream of deleted Us+ None of the percentages are statistically different from random at the level of 95% confidence: p-values for A, G, and C are 0+207, 0+052, and 0+128, respectively+ sibility that the extension of the anchor duplex by a G:U pair does not negatively influence U deletion at that site+ A relatively high proportion of encoded Us in edited regions are located downstream of deletion sites (Fig+ 3A)+ The fraction of deletion sites with a G or a C downstream is nearly what would be expected by chance+ As are present in this position slightly less often than would be expected by a random distribution+ This is unlike the distribution of ribonucleotides downstream of insertion sites, at which As and Gs predominate+ Both upstream and downstream of insertion sites, the ribonucleotides that are found more often than would be expected by chance are those that imply complimentary gRNA bases that do not pair with U+ The profile of ribonucleotides adjacent to deletion sites indicates no such bias+…”

Section: Ribonucleotides Adjacent To Deletion Sitessupporting

confidence: 69%

Sequence bias in edited kinetoplastid RNAs

Burgess

Stuart

2000

RNA

View full text Add to dashboard Cite

Section: Ribonucleotides Adjacent To Deletion Sitessupporting

confidence: 69%

Sequence bias in edited kinetoplastid RNAs

Burgess

Stuart

2000

RNA

View full text Add to dashboard Cite

“…1A did not contain COIderived peptides, but rather represented contamination with several non-mitochondrial T. brucei proteins (data not shown). This is not unexpected, because the COI polypeptide from L. tarentolae was found previously to be refractory to trypsin digestion, 3 and a similar property is anticipated for the T. brucei protein.…”

Section: Mitochondrial Cyb and Coi Proteins Can Be Labeled By Incubatsupporting

confidence: 67%

“…Gene expression in the kinetoplast-mitochondrion of trypanosomatid protists involves a unique post-transcriptional mRNA maturation process, termed RNA editing, whereby Uresidues are inserted to or deleted from a pre-edited transcript, and a translatable reading frame is thus created (1)(2)(3)(4)(5). 12 of the 18 protein-coding genes in the maxicircle component of the mitochondrial or kinetoplast DNA in Trypanosoma brucei or Leishmania tarentolae encode transcripts that require varying degrees of editing for translation competence (6).…”

mentioning

confidence: 99%

The Effect of RNA Interference Down-regulation of RNA Editing 3′-Terminal Uridylyl Transferase (TUTase) 1 on Mitochondrial de Novo Protein Synthesis and Stability of Respiratory Complexes in Trypanosoma brucei

Neboháčová

Maslov

Falick

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Inhibition of RNA editing by down-regulation of expression of the mitochondrial RNA editing TUTase 1 by RNA interference had profound effects on kinetoplast biogenesis in Trypanosoma brucei procyclic cells. De novo synthesis of the apocytochrome b and cytochrome oxidase subunit I proteins was no longer detectable after 3 days of RNAi. The effect on protein synthesis correlated with a decline in the levels of the assembled mitochondrial respiratory complexes III and IV, and also cyanide-sensitive oxygen uptake. The steady-state levels of nuclear-encoded subunits of complexes III and IV were also significantly decreased. Because the levels of the corresponding mRNAs were not affected, the observed effect was likely due to an increased turnover of these imported mitochondrial proteins. This induced protein degradation was selective for components of complexes III and IV, because little effect was observed on components of the F 1 ⅐F 0 -ATPase complex and on several other mitochondrial proteins.Gene expression in the kinetoplast-mitochondrion of trypanosomatid protists involves a unique post-transcriptional mRNA maturation process, termed RNA editing, whereby Uresidues are inserted to or deleted from a pre-edited transcript, and a translatable reading frame is thus created (1-5). 12 of the 18 protein-coding genes in the maxicircle component of the mitochondrial or kinetoplast DNA in Trypanosoma brucei or Leishmania tarentolae encode transcripts that require varying degrees of editing for translation competence (6). These include mRNAs for apocytochrome b (Cyb), 1 subunits II and III of cytochrome c oxidase (COII and COIII, respectively), subunit 6 of ATPase (6), several subunits of NADH dehydrogenase, and a few others. Some transcripts, such as the cytochrome oxidase subunit I (COI) mRNA, do not require editing for translation. The mechanism of editing includes cleavage of RNA at specific editing sites, and the addition or deletion of a defined number of U-residues followed by religation (7,8). The reactions are performed by large protein complexes which include a 3Ј terminal uridylyl transferase (TUTase), an RNA ligase, endo-and exonuclease activities, as well as several additional auxiliary factors of undefined function (9 -12). Subcomplexes exist that contain subsets of proteins and which may specialize in Uaddition or U-deletion (13). The information for selection of editing sites resides in small "guide" RNAs that are mainly encoded in the kinetoplast DNA minicircles (7, 14). These RNA molecules have 3Ј oligo-U tails (15), which are added posttranscriptionally by the RET1 TUTase (16, 17). Down-regulation of RET1 expression by RNA interference (RNAi) results in a decrease in the steady-state abundance of edited transcripts (16) because of an effect on the 3Ј oligo-U tail of the guide RNAs (37).Although editing provides translatable transcripts, inhibition of editing should affect protein synthesis and, consequently, the assembly of respiratory complexes in the kinetoplast. The de novo synthesis of COI and Cyb po...

show abstract

“…RNA editing in trypanosome mitochondria is a unique post-transcriptional maturation process in which uridine residues are inserted and/or deleted at precise sites of mitochondrial mRNAs [38,100,126,384]. Guide RNAs (gRNAs), which are usually transcribed from the kinetoplast DNA minicircles [168], provide the information for the editing.…”

Section: Other Classes Of Small Ncrnamentioning

confidence: 99%

Evolutionary patterns of non-coding RNAs

Bompfünewerer

Flamm

Fried

et al. 2005

Theory in Biosciences

View full text Add to dashboard Cite

A plethora of new functions of non-coding RNAs have been discovered in past few years. In fact, RNA is emerging as the central player in cellular regulation, taking on active roles in multiple regulatory layers from transcription, RNA maturation, and Manuscript January 2005RNA modification to translational regulation. Nevertheless, very little is known about the evolution of this "Modern RNA World" and its components. In this contribution we attempt to provide at least a cursory overview of the diversity of non-coding RNAs and functional RNA motifs in non-translated regions of regular messenger RNAs (mRNAs) with an emphasis on evolutionary questions. This survey is complemented by an in-depth analysis of examples from different classes of RNAs focusing mostly on their evolution in the vertebrate lineage. We present a survey of Y RNA genes in vertebrates, studies of the molecular evolution of the U7 snRNA, the snoRNAs E1/U17, E2, and E3, the Y RNA family, the let-7 microRNA family, and the mRNA-like evf-1 gene. We furthermore discuss the statistical distribution of microRNAs in metazoans, which suggests an explosive increase in the microRNA repertoire in vertebrates. The analysis of the transcription of non-coding RNAs (ncRNAs) suggests that small RNAs in general are genetically mobile in the sense that their association with a hostgene (e.g. when transcribed from introns of a mRNA) can change on evolutionary time scales. The let-7 family demonstrates, that even the mode of transcription (as intron or as exon) can change among paralogous ncRNA.

show abstract

Uridine insertion/deletion RNA editing in trypanosome mitochondria — a review

Cited by 113 publications

References 100 publications

Sequence bias in edited kinetoplastid RNAs

Sequence bias in edited kinetoplastid RNAs

The Effect of RNA Interference Down-regulation of RNA Editing 3′-Terminal Uridylyl Transferase (TUTase) 1 on Mitochondrial de Novo Protein Synthesis and Stability of Respiratory Complexes in Trypanosoma brucei

Evolutionary patterns of non-coding RNAs

Contact Info

Product

Resources

About