bims-mirnam 2026-03-08 papers

Issue of 2026–03–08
four papers selected by
Hana Antonicka, McGill University

Elife. 2026 Mar 02. pii: RP104618. [Epub ahead of print]14

Raw signal segmentation for estimating RNA modification from Nanopore direct RNA sequencing data.

Estimating RNA modifications from Nanopore direct RNA sequencing data is a critical task for the RNA research community. However, current computational methods often fail to deliver satisfactory results due to inaccurate segmentation of the raw signal. We have developed a new method, SegPore, which leverages a molecular jiggling translocation hypothesis to improve raw signal segmentation. SegPore is a pure white-box model with enhanced interpretability, significantly reducing structured noise in the raw signal. We demonstrate that SegPore outperforms state-of-the-art methods, such as Nanopolish and Tombo, in raw signal segmentation across three large benchmark datasets. Moreover, the improved signal segmentation achieved by SegPore enables SegPore+m6Anet to deliver state-of-the-art performance in site-level m6A identification. Additionally, SegPore surpasses baseline methods like CHEUI in single-molecule level m6A identification.

Keywords: Nanopore; RNA modification; alignment; computational biology; human; mouse; raw signal; segmentation; systems biology

DOI: https://doi.org/10.7554/eLife.104618

Bioinformatics. 2026 Feb 28. pii: btag066. [Epub ahead of print]42(3):

Dogme: a nextflow pipeline for reprocessing nanopore RNA and DNA modifications.

Elnaz Abdollahzadeh, Ali Mortazavi.

MOTIVATION: Oxford Nanopore (ONT) sequencing allows for the direct detection of RNA and DNA modifications from unamplified nucleic acids, which is a significant advantage over other platforms. However, the rapid updates to ONT basecalling models and the evolving landscape of computational tools for modification detection bring about challenges for reproducible and standardized analyses. To address these challenges, we developed Dogme to automate basecalling, alignment, modification detection, and transcript quantification. Dogme automates the reprocessing of ONT POD5 files by integrating basecalling using Dorado, read mapping using minimap2 and subsequent analysis steps such as running modkit. The pipeline supports three major types of sequencing data-direct RNA (dRNA), complementary DNA (cDNA), and genomic DNA (gDNA). Dogme facilitates detection of diverse RNA modifications supported by Dorado such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), inosine, pseudouridine, 2'-O-methylation (Nm) and DNA methylation, while concurrently quantifying full-length transcript isoforms LR-Kallisto for transcript quantification for dRNA and cDNA.
RESULTS: We applied Dogme to three separate mouse C2C12 myoblast replicates using direct RNA sequencing on MinION flow cells. We detected 96 603 m6A, 43 476 m5C, 8829 inosine, 10 055 pseudouridine, and 30 320 Nm sites in three biological replicates. The pipeline produced reproducible modification profiles and transcript expression levels across replicates, demonstrating its utility for integrative long-read transcriptomic and epigenomic analyses.
AVAILABILITY AND IMPLEMENTATION: Dogme is implemented in Nextflow and is freely available under the MIT license at https://github.com/mortazavilab/dogme, with documentation provided for installation and usage.

DOI: https://doi.org/10.1093/bioinformatics/btag066

Sci Adv. 2026 Mar 06. 12(10): eaed3579

Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress.

Kenneth Ehses, Jorge P López-Alonso, Odetta Antico, Yannik Lang, Till Rudack, Abdussalam Azem, Miratul M K Muqit, Iban Ubarretxena-Belandia, Rubén Fernández-Busnadiego.

Cells have evolved organelle-specific responses to maintain protein homeostasis (proteostasis). During proteostatic stress, mitochondria down-regulate translation and enhance protein folding, yet the underlying mechanisms remain poorly defined. Here, we used cryo-electron tomography to observe the structural consequences of mitochondrial proteostatic stress within human cells. We detected protein aggregates within the mitochondrial matrix, accompanied by a marked remodeling of cristae architecture. Concomitantly, the number of mitochondrial ribosome complexes was significantly reduced. Mitochondrial Hsp60 (mHsp60), a key protein folding machine, underwent major conformational changes to favor complexes with its co-chaperone mHsp10. We visualized the interactions of mHsp60 with native substrate proteins and determined in vitro mHsp60 cryo-electron microscopy structures enabling nucleotide state assignment of the in situ structures. These data converge on a model of the mHsp60 functional cycle and its essential role in mitochondrial proteostasis. More broadly, our findings reveal structural mechanisms governing mitochondrial protein biosynthesis and their remodeling under proteostatic stress.

DOI: https://doi.org/10.1126/sciadv.aed3579

Proc Natl Acad Sci U S A. 2026 Mar 10. 123(10): e2518495123

Coevolution of RNase P and the ribosome.

Anton S Petrov, Claudia Alvarez-Carreño, Loren Dean Williams, Mark A Ditzler.

Translation is carried out by the most conserved assemblies in biology. Among these assemblies, the ribosome and RNase P are central players. These ancient ribonucleoprotein complexes achieved structural and functional maturity by the last universal common ancestor (LUCA) of life. In prior work, we reconstructed the evolutionary history of the ribosome using its three-dimensional structure, based on accretion and molecular fingerprints that date back to life's earliest stages. Here, we extend our structural phylogenetic framework-based on the accretion model-to RNase P, a ribonucleoprotein responsible for processing pre-tRNAs. By sampling RNase P RNA (RPR) sequences and structures across phylogeny and partitioning them into RNA fragments based on insertion fingerprints, we characterize the state of RPR at LUCA and reconstruct the chronology of its emergence. The chronology reveals that RNase P, like the ribosome, accreted modular RNA elements over evolution, while preserving the structure of preexisting elements, thus maintaining a structural record. We used interactions with tRNA to link and unify the evolutionary trajectories of RPR and rRNA. These results support the view that RNase P and the ribosome coevolved as part of a functionally integrated system. The ancestral catalytic sites of rRNA and RPR formed by the same process, fusion of two stem-elbow-stem elements. Analysis of these two coevolving RNAs also suggests that some of their accreted elements share common ancestry. Application of the accretion model requires correct secondary structures and was successful for RPR only when the traditional secondary structure was corrected by reorganizing a pseudoknot.

Keywords: RNA evolution; origin of life; tranlsation

DOI: https://doi.org/10.1073/pnas.2518495123