Mitochondrial mRNA translation in Apicomplexans:
The phylum Apicomplexa includes pathogenic protozoa like Toxoplasma gondii, which have reduced mitochondrial genomes with only three protein-coding genes and fragmented mitoribosomal rRNAs. In collaboration with Dominique Soldati-Favre's group, we solved the mitoribosome structure from T. gondii, published in Nature Communications (Wang et al., 2024). This study shows that T. gondii assembles over 40 mt-rRNA fragments using nuclear-encoded mitoribosomal proteins and RNA-binding proteins, including four AP2/ERF proteins crucial for mitoribosome integrity. Cryo-EM analysis emphasizes these adaptations and suggests that understanding apicomplexan mitoribosome structure could lead to new therapeutic strategies for mitochondrial translation.
Ultra selective trans-RNA-mediated mRNA translation:
We recently completed a study with Shu-Bing Qian's group at Cornell to design trans-RNAs capable of selectively initiating various Open Reading Frames (ORFs), published in Nature Biotechnology (Jia et al., 2025). This study introduces capped trans-RNAs that activate mRNAs for translation by directing ribosomes to specific start codons without altering sequences. These trans-RNAs enhance ribosome loading and can initiate translation of circular RNAs lacking internal ribosome entry sites. In vivo results demonstrate successful programmable translation of endogenous genes in mouse liver, revealing natural transcripts that similarly activate mRNA translation.
Kozak sequence and m6A modifications:
The N6-methyladenosine (m6A) modification is unevenly distributed on mRNAs, with 5' untranslated regions (5' UTRs) showing the least presence. We published an article in Molecular Cell (Guca et al., 2024) with the Zoya Ignatova group investigating how m6A affects translation initiation. The study shows that a single m6A does not influence translation yields or start codon recognition, even under oxidative stress. Cryo-EM analysis reveals that m6A interacts with initiation factor eIF2α but contributes only marginally to energy. Thus, m6A stabilizes the initiation complex slightly without significantly impacting translation dynamics in normal or stressed conditions.
Fast and efficient method to purify mRNA translation complexes:
We developed a new method, RNA affinity purification using poly-lysine (RAPPL), to efficiently purify ribosomes, published in Nature Communications (Erath et al., 2025). This rapid and cost-effective method overcomes challenges of traditional techniques. It proves useful for studying resistance mechanisms in uropathogenic Escherichia coli and generating a 2.7-Å cryo-EM ribosome structure from Cryptococcus neoformans. By minimizing the biological material and isolation time required, RAPPL offers a versatile platform for exploring ribosomal function and antibiotic resistance.
