bims-mitran 2026-06-14 papers

Issue of 2026–06–14
two papers selected by
Andreas Kohler, Umeå University

Biochim Biophys Acta Mol Cell Res. 2026 Jun 09. pii: S0167-4889(26)00069-8. [Epub ahead of print] 120171

Folding the message: mRNA structure as a regulatory layer of human mitochondrial gene expression.

Ahram Ahn, Seungwoo Hong, Michele Brischigliaro, Flavia Fontanesi, Antoni Barrientos.

Mammalian mitochondrial gene expression operates within an unusually compact genomic architecture in which most regulatory information must be encoded within or immediately adjacent to protein-coding sequences. In this context, mitochondrial mRNAs function not merely as templates for translation but as structured molecules whose folding landscape contributes to multiple stages of gene expression. Recent advances in chemical probing, mutational profiling, and mitoribosome profiling have begun to disclose the human mitochondrial mRNA structurome in its native organellar context, revealing a transcriptome that is broadly accessible yet punctuated by localized structural elements and alternative conformational states. These studies indicate that RNA structure contributes to translation initiation on leaderless transcripts, elongation kinetics, translational coupling across bicistronic junctions, and dynamic remodeling during membrane protein synthesis. They also highlight the role of RNA-binding proteins, including LRPPRC-SLIRP and related factors, in maintaining a translation-competent folding environment. In this review, we discuss the structural organization of mitochondrial mRNAs, the experimental approaches that enabled its analysis, and emerging mechanistic links between RNA folding, translational regulation, and respiratory chain biogenesis. We further discuss how alterations in mt-mRNA structure may represent an underappreciated determinant of mitochondrial disease and consider implications for future diagnostic and therapeutic strategies.

Keywords: Bicistronic transcripts; Mitochondrial RNA folding; Mitochondrial RNA processing; Mitochondrial RNA structurome; Mitochondrial gene expression; Mitochondrial translation

DOI: https://doi.org/10.1016/j.bbamcr.2026.120171

Proc Natl Acad Sci U S A. 2026 Jun 16. 123(24): e2534946123

Expression of four mitochondrial tRNAs from only two loci.

Jessica M Warren, Kasavajhala V S K Prasad, Anistynn M Mendez, Stephanie Temnyk, John P McCutcheon.

Transfer RNAs (tRNAs) are among the few genes retained in animal mitochondrial genomes after more than a billion years of gene loss. These ancient bacterial vestiges are often structurally aberrant and less stable than their bacterial or cytosolic tRNA counterparts. In some lineages, mitochondrial tRNAs (mt-tRNAs) have become so truncated that the loss of one or both arms has expanded our understanding of what constitutes a functional tRNA. Here, we report another radical departure from canonical tRNA gene architecture: two overlapping tRNAs produced from opposite strands of the same locus. These "mirror" tRNA pairs eliminate the need to retain separate loci for all tRNA genes, as a single locus can produce tRNAs to decode two different amino acids. We show that these mirror tRNAs are aminoacylated and demonstrate their presence in mitoribosomes. Furthermore, mirror tRNAs display strand-specific patterns of nucleotide modification and RNA editing, reflecting specific posttranscriptional maturation that depends on transcriptional orientation. This demonstration of functional, bidirectional tRNA expression reveals an unexpected strategy by which mitochondrial genomes maintain a complete set of tRNAs in the face of unrelenting gene loss. The presence of mirror tRNAs has broad implications for the evolution of tRNA-interacting enzymes, mitochondrial biology, and even the origins of the protein synthesis machinery itself.

Keywords: bidirectional transcription; mitochondrial genome evolution; mitochondrial tRNAs

DOI: https://doi.org/10.1073/pnas.2534946123