Dataset Information

Guide RNA-binding complex from mitochondria of trypanosomatids.

ABSTRACT: In the mitochondria of trypanosomatids, the majority of mRNAs undergo massive uracil-insertion/deletion editing. Throughout the processes of pre-mRNA polyadenylation, guide RNA (gRNA) uridylylation and annealing to mRNA, and editing reactions, several multiprotein complexes must engage in transient interactions to produce a template for protein synthesis. Here, we report the identification of a protein complex essential for gRNA stability. The gRNA-binding complex (GRBC) interacts with gRNA processing, editing, and polyadenylation machineries and with the mitochondrial edited mRNA stability (MERS1) factor. RNAi knockdown of the core subunits, GRBC1 and GRBC2, led to the elimination of gRNAs, thus inhibiting mRNA editing. Inhibition of MERS1 expression selectively abrogated edited mRNAs. Homologous proteins unique to the order of Kinetoplastida, GRBC1 and GRBC2, form a stable 200 kDa particle that directly binds gRNAs. Systematic analysis of RNA-mediated and RNA-independent interactions involving the GRBC and MERS1 suggests a unified model for RNA processing in the kinetoplast mitochondria.

SUBMITTER: Weng J

PROVIDER: S-EPMC2645705 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Guide RNA-binding complex from mitochondria of trypanosomatids.

Weng James J Aphasizheva Inna I Etheridge Ronald D RD Huang Lan L Wang Xiaorong X Falick Arnold M AM Aphasizhev Ruslan R

Molecular cell 20081001 2

In the mitochondria of trypanosomatids, the majority of mRNAs undergo massive uracil-insertion/deletion editing. Throughout the processes of pre-mRNA polyadenylation, guide RNA (gRNA) uridylylation and annealing to mRNA, and editing reactions, several multiprotein complexes must engage in transient interactions to produce a template for protein synthesis. Here, we report the identification of a protein complex essential for gRNA stability. The gRNA-binding complex (GRBC) interacts with gRNA proc ...[more]

PMID: 18951088

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Project description:BackgroundTrypanosomatid parasites are a group of protozoans that cause devastating diseases that disproportionately affect developing countries. These protozoans have developed several mechanisms for adaptation to survive in the mammalian host, such as extensive expansion of multigene families enrolled in host-parasite interaction, adaptation to invade and modulate host cells, and the presence of aneuploidy and polyploidy. Two mechanisms might result in "complex" isolates, with more than two haplotypes being present in a single sample: multiplicity of infections (MOI) and polyploidy. We have developed and validated a methodology to identify multiclonal infections and polyploidy using whole genome sequencing reads, based on fluctuations in allelic read depth in heterozygous positions, which can be easily implemented in experiments sequencing genomes from one sample to larger population surveys.ResultsThe methodology estimates the complexity index (CI) of an isolate, and compares real samples with simulated clonal infections at individual and populational level, excluding regions with somy and gene copy number variation. It was primarily validated with simulated MOI and known polyploid isolates respectively from Leishmania and Trypanosoma cruzi. Then, the approach was used to assess the complexity of infection using genome wide SNP data from 497 trypanosomatid samples from four clades, L. donovani/L. infantum, L. braziliensis, T. cruzi and T. brucei providing an overview of multiclonal infection and polyploidy in these cultured parasites. We show that our method robustly detects complex infections in samples with at least 25x coverage, 100 heterozygous SNPs and where 5-10% of the reads correspond to the secondary clone. We find that relatively small proportions (≤ 7%) of cultured trypanosomatid isolates are complex.ConclusionsThe method can accurately identify polyploid isolates, and can identify multiclonal infections in scenarios with sufficient genome read coverage. We pack our method in a single R script that requires only a standard variant call format (VCF) file to run ( https://github.com/jaumlrc/Complex-Infections ). Our analyses indicate that multiclonality and polyploidy do occur in all clades, but not very frequently in cultured trypanosomatids. We caution that our estimates are lower bounds due to the limitations of current laboratory and bioinformatic methods.

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Guide RNA-binding complex from mitochondria of trypanosomatids.

Publications

Guide RNA-binding complex from mitochondria of trypanosomatids.

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