Identification of human mitochondrial RNA cleavage sites and candidate RNA processing factors DOI Creative Commons
Guillermo Carbajosa, Aminah T. Ali, Alan Hodgkinson

et al.

BMC Biology, Journal Year: 2022, Volume and Issue: 20(1)

Published: July 22, 2022

The human mitochondrial genome is transcribed as long strands of RNA containing multiple genes, which require post-transcriptional cleavage and processing to release functional gene products that play vital roles in cellular energy production. Despite knowledge implicating processes pathologies such cancer, cardiovascular disease diabetes, very little known about the way their function varies on a population level what drives changes these ultimately influence risk. Here, we develop method detect quantify events from standard sequencing data apply this approach whole blood > 1000 samples across independent cohorts.We 54 putative sites not only map boundaries, short ends modification sites, but also occur at internal positions, suggesting novel junctions. Inferred rates correlate with mitochondrial-encoded expression individuals, an impact downstream processes. Furthermore, by comparing inferred nuclear genetic variation expression, implicate genes modulating (e.g. MRPP3, TBRG4 FASTKD5), including potentially role for RPS19 influencing site near MTATP6-COX3 junction validate using shRNA knock down data.We identify junctions associated processing, well newly implicated processes, potential phenotypes These results highlight complexity transcriptome point mechanisms through nuclear-encoded can key

Language: Английский

Organization and expression of the mammalian mitochondrial genome DOI
Oliver Rackham, Aleksandra Filipovska

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(10), P. 606 - 623

Published: April 22, 2022

Language: Английский

Citations

98
Mechanisms and regulation of human mitochondrial transcription DOI
Benedict G. Tan, Claes M. Gustafsson, Maria Falkenberg

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(2), P. 119 - 132

Published: Oct. 2, 2023

Language: Английский

Citations

42
A kinetic dichotomy between mitochondrial and nuclear gene expression processes DOI
Erik McShane, Mary Couvillion, Robert Ietswaart

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(8), P. 1541 - 1555.e11

Published: March 18, 2024

Language: Английский

Citations

23
Advances in human pre-tRNA maturation : TRMT10C and ELAC2 in focus DOI Creative Commons

Juhi Sikarwar,

Vincent Meynier, Carine Tisné

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 168989 - 168989

Published: Feb. 1, 2025

Language: Английский

Citations

1
Metal Complexes in Target-Specific Anticancer Therapy: Recent Trends and Challenges DOI Creative Commons
Gemechu Shumi, Tegene Desalegn, Taye B. Demissie

et al.

Journal of Chemistry, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 19

Published: May 17, 2022

Cancer is characterized by abnormal cell differentiation in or on the part of body. The most commonly used chemotherapeutic drugs are developed to target rapidly dividing cells, such as cancer but they also damage healthy epithelial cells. This has serious consequences for normal cells and become responsible development various disorders. Several strategies delivering cytotoxic cancerous sites that limit systemic toxicity other adverse effects have recently been evolved. Among them, biomolecule-conjugated metal complexes-based targeting shown tremendous advantages therapy. review focuses several chemoselective biomolecules-bound complexes prospective therapy-targeted agents. In this review, we presented details extra- intracellular mechanisms We addressed current clinical issues recent therapeutic targeted therapy may pave a way future direction

Language: Английский

Citations

35
The human mitochondrial genome contains a second light strand promoter DOI Creative Commons
Benedict G. Tan, Christian D. Mutti, Yonghong Shi

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(19), P. 3646 - 3660.e9

Published: Aug. 30, 2022

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism supply cells with adequate levels of adenosine triphosphate. Central this process is the idea that replication primers gene products both arise via transcription from single light strand promoter (LSP) such primer formation can influence expression, no consensus as how regulated. Here, we report discovery second (LSP2) humans, features characteristic bona fide promoter. We propose position LSP2 on allows expression orchestrated two distinct sites, which expands our long-held understanding humans.

Language: Английский

Citations

35
Mitochondrial DNA quality control in the female germline requires a unique programmed mitophagy DOI Creative Commons

Jonathan M. Palozzi,

Swathi P. Jeedigunta,

Anastasia V. Minenkova

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1809 - 1823.e6

Published: Nov. 1, 2022

Language: Английский

Citations

28
The human mitochondrial mRNA structurome reveals mechanisms of gene expression DOI
J. Conor Moran, Amir Brivanlou, Michele Brischigliaro

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6706)

Published: July 18, 2024

The human mitochondrial genome encodes crucial oxidative phosphorylation system proteins, pivotal for aerobic energy transduction. They are translated from nine monocistronic and two bicistronic transcripts whose native structures remain unexplored, posing a gap in understanding gene expression. In this work, we devised the dimethyl sulfate mutational profiling with sequencing (mitoDMS-MaPseq) method applied detection of RNA folding ensembles using expectation-maximization (DREEM) clustering to unravel messenger (mt-mRNA) structurome wild-type (WT) leucine-rich pentatricopeptide repeat-containing protein (LRPPRC)-deficient cells. Our findings elucidate LRPPRC's role as holdase contributing maintaining mt-mRNA efficient translation. structural insights WT mitochondria, coupled metabolic labeling, unveil potential mRNA-programmed translational pausing distinct programmed ribosomal frameshifting mechanism. data define critical layer expression regulation. These maps provide reference studying diverse physiological pathological contexts.

Language: Английский

Citations

8
A random forest-based metabolic risk model to assess the prognosis and metabolism-related drug targets in ovarian cancer DOI

Haoxin Zhang,

Chi Meng, Dongqing Su

et al.

Computers in Biology and Medicine, Journal Year: 2022, Volume and Issue: 153, P. 106432 - 106432

Published: Dec. 16, 2022

Language: Английский

Citations

20
High expression of novel biomarker TBRG4 promotes the progression and invasion of oral squamous cell carcinoma DOI

Abilasha Ramasubramanian,

Pratibha Ramani, Balachander Kannan

et al.

Journal of Oral Pathology and Medicine, Journal Year: 2023, Volume and Issue: 52(8), P. 738 - 745

Published: Aug. 3, 2023

Abstract Background Transforming growth factor β regulator 4 (TBRG4) is a potential prognostic indicator in various cancers, especially squamous cell carcinomas, and associated with disease amelioration poor outcomes. The study aimed to assess the expression pattern of TBRG4 patients operable oral carcinoma (OSCC) understand its role tumour progression using indicators outcome like stage, grade, nodal metastasis, invasion. Methods was assessed by analyzing 51 cancer adjacent non‐cancerous tissues OSCC quantitative real‐time PCR, Western blot. also analysed Cancer Genome Atlas Head–Neck Squamous Cell Carcinoma (TCGA‐HNSC) dataset UALCAN tool ( http://ualcan.path.uab.edu/ ). relationship between patient's prognosis Kaplan–Meier plotter. Results Both mRNA protein levels were significantly increased tissues. TBGR4 advanced stages (III IV) worst invasion (WPOI‐4 5). High reduced overall survival p = 0.011). In addition, analysis gene clinical data from TCGA, identified that highly expressed HPV negative positively correlated survival. Conclusion present suggests high might serve as novel biomarker for HPV‐negative OSCC, which can be validated future additional investigations larger cohorts along functional studies.

Language: Английский

Citations

12