Mitochondrial RNA editing in Trypanoplasma borreli: New tools, new revelations

Gerasimov, Evgeny S.; Afonin, Dmitry A.; Korzhavina, Oksana A.; Lukeš, Julius; Low, Ross; Hall, Neil; Yurchenko, Vyacheslav; Zimmer, Sara L.

doi:10.1016/j.csbj.2022.11.023

Cited by 2 publications

(8 citation statements)

References 81 publications

(153 reference statements)

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“…T-Aligner failed to reconstruct edited ORFs for all identified complex I subunit cryptogenes ( ND3 , ND7 , ND8 , ND9 , MURF2 , and the putative ND4L and ND6 homologues G3 and G4 , respectively ( 84 , 85 )). To the best of our knowledge, their transcripts are edited in all investigated trypanosomatids, although corresponding genes are absent in the distantly related kinetoplastid Trypanoplasma borreli ( 24 ).…”

Section: Resultsmentioning

confidence: 99%

“…Both poly(A)-enriched total RNA libraries (libraries 3 and 4, Supplementary Table S1 ) and the kRNA-enriched library (library 5, Supplementary Table S1 ) were independently mapped to the maxicircle using Burrows-Wheeler Aligner (BWA) v. 0.7.17 ( 47 ) and alignments were processed with SAMTools v. 1.17 ( 48 ) and BEDTools v. 2.30.0 ( 49 ) to produce initial RNA coverage profiles using unedited reads only. T-Aligner v. 4.0.5f ( 24 ) was used to reconstruct cryptogene ORFs and capture levels of both edited and unedited mapped reads across the maxicircle coding region as reported previously ( 40 ). To assemble the cryptogene A6 specifically, reads of the small RNA library (library 6, Supplementary Table S1 ) were added to the other RNA libraries and the search depth was increased to its maximum level.…”

Section: Methodsmentioning

confidence: 99%

“…Minicircle- and maxicircle-encoded gRNAs were initially annotated using ‘findgrna’ tool from T-Aligner that predicts gRNA coding genes with a minicircle:mRNA alignment procedure used previously ( 24 , 40 ).…”

Section: Methodsmentioning

confidence: 99%

“…For example, mRNA encoding the NADH:ubiquinone oxidoreductase subunit 5 ( ND5 ) of the electron transport chain (ETC) complex I requires editing in the free-living bodonid Bodo saltans ( 22 ), but not in trypanosomatids ( 23 ). Similarly, the ETC complex IV mRNA for cytochrome c oxidase subunit I ( COI ) is not edited in any species but Trypanoplasma borreli ( 24 ). Cryptogenes ND8 and COIII encoding subunits of the ETC complexes I and IV, respectively, are often pan-edited, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…To address this, we developed a specialized toolkit called T-Aligner ( 20 ), which allows exhaustive mapping of edited reads (containing U-indels) to their cryptogenes of origin and efficient reconstructing of edited ORFs. Moreover, we have established a pipeline to map gRNA:mRNA interactions from minicircle sequences and RNA-seq reads, and to build complete gene editing maps ( 24 , 32 ).…”

Section: Introductionmentioning

confidence: 99%

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Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment

Afonin,

Gerasimov,

Škodová-Sveráková

et al. 2024

Nucleic Acids Research

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The canonical stop codons of the nuclear genome of the trypanosomatid Blastocrithidia nonstop are recoded. Here, we investigated the effect of this recoding on the mitochondrial genome and gene expression. Trypanosomatids possess a single mitochondrion and protein-coding transcripts of this genome require RNA editing in order to generate open reading frames of many transcripts encoded as ‘cryptogenes’. Small RNAs that can number in the hundreds direct editing and produce a mitochondrial transcriptome of unusual complexity. We find B. nonstop to have a typical trypanosomatid mitochondrial genetic code, which presumably requires the mitochondrion to disable utilization of the two nucleus-encoded suppressor tRNAs, which appear to be imported into the organelle. Alterations of the protein factors responsible for mRNA editing were also documented, but they have likely originated from sources other than B. nonstop nuclear genome recoding. The population of guide RNAs directing editing is minimal, yet virtually all genes for the plethora of known editing factors are still present. Most intriguingly, despite lacking complex I cryptogene guide RNAs, these cryptogene transcripts are stochastically edited to high levels.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment

Afonin,

Gerasimov,

Škodová-Sveráková

et al. 2024

Nucleic Acids Research

Self Cite

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Trypanosome RNA helicase KREH2 differentially controls non-canonical editing and putative repressive structure via a novel proposed ‘bifunctional’ gRNA in mRNA A6

Meehan,

McDermott,

Ivens

et al. 2023

Nucleic Acids Research

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U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria is directed by guide RNAs (gRNAs). This editing may developmentally control respiration in bloodstream forms (BSF) and insect procyclic forms (PCF). Holo-editosomes include the accessory RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C), but the specific proteins controlling differential editing remain unknown. Also, RNA editing appears highly error prone because most U-indels do not match the canonical pattern. However, despite extensive non-canonical editing of unknown functions, accurate canonical editing is required for normal cell growth. In PCF, REH2C controls editing fidelity in RESC-bound mRNAs. Here, we report that KREH2, a REH2C-associated helicase, developmentally controls programmed non-canonical editing, including an abundant 3′ element in ATPase subunit 6 (A6) mRNA. The 3′ element sequence is directed by a proposed novel regulatory gRNA. In PCF, KREH2 RNAi-knockdown up-regulates the 3′ element, which establishes a stable structure hindering element removal by canonical initiator-gRNA-directed editing. In BSF, KREH2-knockdown does not up-regulate the 3′ element but reduces its high abundance. Thus, KREH2 differentially controls extensive non-canonical editing and associated RNA structure via a novel regulatory gRNA, potentially hijacking factors as a ‘molecular sponge’. Furthermore, this gRNA is bifunctional, serving in canonical CR4 mRNA editing whilst installing a structural element in A6 mRNA.

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Mitochondrial RNA editing in Trypanoplasma borreli: New tools, new revelations

Cited by 2 publications

References 81 publications

Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment

Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment

Trypanosome RNA helicase KREH2 differentially controls non-canonical editing and putative repressive structure via a novel proposed ‘bifunctional’ gRNA in mRNA A6

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