bims-mirnam 2026-04-19 papers

bims-mirnam

Biomed News

on Mitochondrial RNA metabolism

Issue of 2026–04–19
seven papers selected by
Hana Antonicka, McGill University

Mitochondrial translation elongation controls OXPHOS biogenesis by coordinating synthesis and folding of mitochondrially encoded proteins.
Asymmetric dimeric assembly of Suv3 helicase facilitates processive RNA unwinding.
Characterizations of G-Quadruplex RNA-Protein Interactions in Living Cells.
Cytoplasmic localization of pseudouridine synthase 7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance.
Targeting Tumour Microtubes to Disrupt Glioma Networks.
Development of Universal Mass Exclusion List (UMEL) for RNA modification mapping.
MitoChontrol: Adaptive mitochondrial filtering for robust single-cell RNA sequencing quality control.

Mol Cell. 2026 Apr 16. pii: S1097-2765(26)00193-0. [Epub ahead of print]86(8): 1511-1528.e12

Mitochondrial translation elongation controls OXPHOS biogenesis by coordinating synthesis and folding of mitochondrially encoded proteins.

Lvxin Xie, Shuchao Ren, Li Zhang, Ziqing Wang, Tong Wu, Qing Dai, Shikun Xiang, Zhihua Qian, Yufan Xian, Shutong Xu, Xiao-Lin Chen, Chuan He, Yi Liu, Zhipeng Zhou.

  Mitochondria generate ATP through oxidative phosphorylation (OXPHOS), with core structural subunits encoded by mitochondrial DNA (mtDNA) and translated by mitochondrial ribosomes. However, how mitochondrial translation elongation influences OXPHOS biogenesis remains unclear. Here, we show that in Neurospora crassa, the mitochondrial ribosomal RNA (rRNA) methyltransferase 1 (MRM1) promotes OXPHOS biogenesis by repressing translation elongation independently of its catalytic activity. The N-terminal intrinsically disordered region (IDR) of MRM1 binds simultaneously to mitochondrial ribosomes and mRNAs. Disrupting either interaction accelerates elongation and enhances synthesis of mtDNA-encoded OXPHOS subunits but impairs their co-translational folding and membrane insertion. Pharmacological slowing of mitochondrial translation partially alleviates these defects. The MRM1 IDR is conserved in Ascomycete fungi and is essential for plant infection by Magnaporthe oryzae. Together, our findings identify translation elongation control as a mechanism coordinating mitochondrial protein synthesis and folding during OXPHOS biogenesis and MRM1 as a potential target for broad-spectrum antifungal strategies.

Keywords:  Magnaporthe oryzae; Neurospora crassa; mitochondrial rRNA methyltransferase; mitochondrial translation; oxidative phosphorylation; protein folding; translation elongation

DOI:  https://doi.org/10.1016/j.molcel.2026.03.017
Nat Commun. 2026 Apr 15.

Asymmetric dimeric assembly of Suv3 helicase facilitates processive RNA unwinding.

Malay Patra, Monika Jain, Yi-Ching Li, Yi-Ping Chen, Bagher Golzarroshan, Hanna S Yuan.

Human Suv3 is a dimeric helicase that collaborates with the exoribonuclease PNPase to mediate RNA decay and surveillance in mitochondria. Despite its pivotal role in maintaining mitochondrial homeostasis, the molecular mechanism underlying Suv3-mediated RNA unwinding has remained elusive. Here, we present near-atomic-resolution cryogenic electron microscopy structures of Suv3 captured in four functional states: the apo form, two binary complexes with ADP and single-stranded RNA (ssRNA), and a ternary complex with ssRNA and an ATP analog (AMP-PNP). These structures reveal an unexpected asymmetric dimeric organization, in which only one of the two protomers engages in the initial binding of ADP, ssRNA, or both ssRNA and AMP-PNP. Complementary biochemical analyses demonstrate that Suv3 dimerization significantly enhances RNA-binding and unwinding efficiency in an ATP-hydrolysis-dependent manner. Together, these findings provide key insights into the dimeric architecture of Suv3 and establish a mechanistic framework for its coordinated function in processive RNA unwinding.

DOI: https://doi.org/10.1038/s41467-026-71901-2
Anal Chem. 2026 Apr 17.

Characterizations of G-Quadruplex RNA-Protein Interactions in Living Cells.

Feng Tang, Xiaochen Liang, Douglas F Porter, Weili Miao, Kevin Maehlmann, Jun Yuan, Paul A Khavari, Yinsheng Wang.

RNA guanine quadruplexes (rG4s) are noncanonical nucleic acid structures that contribute to diverse cellular functions and disease mechanisms. Defining the proteins that interact with rG4s (rG4IPs) is essential for elucidating their biological roles. Here, we build on the RNA-protein interaction detection (RaPID) platform to develop G4-RaPID, a tailored chemoproteomic strategy for the unbiased profiling of rG4IPs in living cells. Using G4-RaPID, we identified 105 candidate rG4IPs that were commonly enriched across three distinct rG4 sequences. Biochemical analyses confirmed that recombinant hnRNPA0, CHD4, and IGF2BP1 proteins directly bind rG4 structures in vitro. In addition, CLIP-seq experiments revealed significant enrichment of hnRNPA0 binding at endogenous rG4 loci. Luciferase reporter assays further demonstrated that hnRNPA0 engages the rG4 in the 5' UTR of NRAS mRNA to negatively regulate its translation. Together, these results establish G4-RaPID as a robust approach for mapping rG4-protein interactions in living cells and document hnRNPA0-rG4 recognition as a regulatory mechanism controlling NRAS mRNA translation.

DOI: https://doi.org/10.1021/acs.analchem.6c00902
Nat Commun. 2026 Apr 17.

Cytoplasmic localization of pseudouridine synthase 7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance.

Minli Ruan, Sean M Engels, Matthew R Burroughs, Xiaoyan Li, Rosella Stower, Talia Tzadikario, Connor Powell, Dylan Bloch, Oleksandra Fanari, Stuart Akeson, Daniel E Eyler, Chase A Weidmann, Sara Rouhanifard, Miten Jain, Lydia M Contreras, Kristin S Koutmou.

Pseudouridine (Ψ) is an abundant post-transcriptional modification found across all classes of RNA. It is widely speculated that Ψ inclusion in messenger RNAs (mRNAs) might provide an avenue for cells to control gene expression post-transcriptionally. Here we demonstrate that one of the principal mRNA pseudouridylating enzymes, pseudouridine synthase 7 (PUS7), exhibits a stress-induced accumulation in the cytoplasm of yeast and human epithelial lung cells. Stress-induced and cytoplasmic localization of PUS7 promotes Ψ-incorporation into hundreds of mRNA targets. In contrast, the modification status of tRNA sites targeted by PUS7 (Ψ13 and Ψ35) is unperturbed. Furthermore, engineered PUS7 cytoplasmic localization increases cellular fitness under reactive oxygen species (ROS) and divalent metal ion stress. Quantitative proteomics reveal a reshaping of the proteome upon PUS7 relocalization under stress. Collectively, our data demonstrate that PUS7 localization alters mRNA pseudouridylation patterns, reshapes the proteome, and influences cellular fitness.

DOI: https://doi.org/10.1038/s41467-026-71654-y
Res Sq. 2026 Apr 07. pii: rs.3.rs-8605748. [Epub ahead of print]

Targeting Tumour Microtubes to Disrupt Glioma Networks.

Jeremy Rich, Tengfei Huang, Po Zhang, Suchet Taori, Shuai Wang, Donghai Wang, Zhiye Chen, Huairui Yuan, Xujia Wu, Tingting Duan, Fanen Yuan, Weichi Wu, Rui Wang, Huan Li, Hailong Mi, Deguan Lv, Deobrat Dixit, Frank Winkler, Qiulian Wu.

Glioma cells form multicellular communication networks through tumour microtubes (TMs), integrating tumour-tumour and neuron-tumour connectivity to sustain growth and therapy resistance. Underlying molecular regulation of TMs and potential targeting strategies have proven elusive. Here, we demonstrate that glioma stem cells (GSCs) preferentially grow TMs, which locally synthesize neurotransmitter receptors and metabolic enzymes to support network communication. Coordinated proteomics and functional screening of TMs identified inner mitochondrial component, FASTKD2, as essential to local protein synthesis. Targeting FASTKD2 attenuates tumour stemness and growth, disrupting coordinated mitochondrial RNA metabolism in TMs, which sustains intercellular communication and tumour proliferation. Structure-function screening revealed antibiotic linezolid inhibited FASTKD2 interactions with mitochondrial RNA, thereby disrupting tumour network communication and augmenting efficacy of therapies targeting neuronal stimulation of tumour cells. Collectively, tumour cells coopt features of neuronal cell biology, including localized protein synthesis, to reinforce TM-mediated glioma network communication, generating therapeutic vulnerabilities.

DOI: https://doi.org/10.21203/rs.3.rs-8605748/v1
RNA. 2026 Apr 16. pii: rna.080901.125. [Epub ahead of print]

Development of Universal Mass Exclusion List (UMEL) for RNA modification mapping.

Asif Rayhan, Patrick A Limbach, Balasubrahmanyam Addepalli.

  Understanding the location of modified nucleosides in RNA sequences is crucial to understanding their biochemical significance. Mapping the sequence location of modified nucleosides from low abundance RNAs is challenging. Here, we report the development of a liquid chromatography tandem mass spectrometry (LC-MS/MS) exclusion list strategy that enhances sequence information from modified oligonucleotides. This approach, compatible with standard RNA modification mapping methods that utilize LC-MS/MS, enables the exclusion of any unmodified oligonucleotide from fragmentation during MS/MS thereby enabling enhanced dissociation of modified oligonucleotides. This universal exclusion list is applicable to natural RNAs of any type from any organism. We find this approach generates at least 10% more mapped RNase T1 digestion products than using DDA alone. To demonstrate the broad utility of this approach for discovery-based analyses, RNA modification mapping of total tRNAs from four distinct organisms spanning both prokaryotic and eukaryotic domains was conducted.

Keywords:  RNA mass mapping; RNA modification mapping; modified nucleoside; tRNA modification; universal mass exclusion list

DOI:  https://doi.org/10.1261/rna.080901.125
bioRxiv. 2026 Apr 07. pii: 2026.04.04.716517. [Epub ahead of print]

MitoChontrol: Adaptive mitochondrial filtering for robust single-cell RNA sequencing quality control.

Caitlin Strassburg, Danielle Pitlor, Aatur D Singhi, Rachel A Gottschalk, Shikhar Uttam.

Summary: Mitochondrial transcript abundance is a standard quality control metric in single-cell RNA sequencing, but fixed percentage thresholds fail to account for the substantial variation in mitochondrial content across cell types and tissues, risking both retention of compromised cells and exclusion of transcriptionally active viable cell populations. We present MitoChontrol, a cell-type-aware probabilistic framework for mitochondrial quality control that models the mitochondrial transcript fraction within transcriptionally coherent clusters as a Gaussian mixture distribution. Compromised-cell components are identified from the upper tail of each cluster-specific distribution, and filtering thresholds are defined as the point at which the posterior probability of cellular compromise exceeds a user-definded confidence value. Applied to controlled perturbation experiments and a pancreatic ductal adenocarcinoma single-cell dataset, MitoChontrol selectively removes transcriptionally compromised cells while preserving biologically elevated but viable populations, outperforming fixed-threshold and outlier-based approaches.
Availability and Implementation: MitoChontrol is implemented in Python and integrates directly with AnnData-based workflows. It is freely available under the GNU General Public License v3 (GPL-3.0) at: https://github.com/uttamLab/MitoChontrol (DOI: https://doi.org/10.5281/zenodo.19423054 ).

DOI: https://doi.org/10.64898/2026.04.04.716517