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Editing of Trypanosoma brucei maxicircle CR5 mRNA generates variable carboxy terminal predicted protein sequences
L K Read1, K D Wilson, P J Myler
1Seattle Biomedical Research Institute, WA 98109-1651.
Abstract:
RNA editing post-transcriptionally modifies several mRNAs from the maxicircle of kinetoplastid parasites by addition and removal of uridine residues. We report here that maxicircle CR5 transcripts of Trypanosoma brucei are edited in two domains separated by an eight nucleotide sequence that remains unedited. The large 5' domain is edited to a consensus sequence while the smaller 3' domain is edited to multiple final sequences. In all, 205-217 Us are inserted and 13-16 encoded uridines are deleted from the CR5 mRNA, producing a mature transcript 75-80% larger than the unedited transcript. The edited RNAs predict small, highly hydrophobic proteins. The carboxy terminal 15-30% of these predicted proteins have multiple different amino acid sequences as a result of the variable edited 3' mRNA sequence, but these fall into two families of sequence. Limited amino acid sequence and hydrophobicity profile similarities suggest that the protein encoded by edited CR5 mRNA may be a subunit of NADH dehydrogenase.
Insights
Kinetoplastid parasites like Trypanosoma brucei extensively edit CR5 messenger RNAs (mRNAs) by adding uridines. This RNA editing process results in larger, modified mRNAs that encode novel proteins potentially involved in NADH dehydrogenase.
Area of Science:
- Molecular Biology
- Parasitology
- Genetics
Background:
- RNA editing is a crucial post-transcriptional modification in kinetoplastids.
- Maxicircle transcripts undergo significant uridine insertion and deletion.
- CR5 mRNA editing in Trypanosoma brucei involves distinct domains.
Purpose of the Study:
- To investigate the specifics of CR5 mRNA editing in Trypanosoma brucei.
- To characterize the edited sequences and resulting protein products.
- To explore the functional implications of CR5 mRNA editing.
Main Methods:
- Analysis of maxicircle CR5 transcripts from Trypanosoma brucei.
- Sequencing and comparison of edited and unedited CR5 mRNA.
- Bioinformatic prediction of protein structure and function.
Main Results:
- CR5 mRNA editing occurs in two domains, with a conserved unedited region.
- Extensive uridine insertion (205-217 Us) and deletion (13-16 Us) were observed.
- Edited CR5 mRNA yields proteins with variable C-terminal sequences but conserved hydrophobicity, suggesting a role in NADH dehydrogenase.
Conclusions:
- RNA editing significantly alters CR5 mRNA structure and protein coding potential.
- The variable protein sequences suggest adaptability or complex function.
- The predicted protein is likely a subunit of NADH dehydrogenase, highlighting the importance of RNA editing in parasite metabolism.