bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.11.04.565600

The highly abundant mRNA m1A modification: a new layer of gene regulation in dinoflagellates

LI, C.·LI, Y.·GUO, J.·WANG, Y.·SHI, X.·ZHANG, Y.·LIANG, N.·YUAN, J.·XU, J.·Chen, H.
View original source ↗Export metadata ↓

Abstract

The N1-methyladenosine (m1A) is a positively charged RNA modification known to disrupt base pairing and influence RNA stability. Despite its limited presence in the mRNA of various organism models, including yeast, mouse, and human, the exact processes of m1A biosynthesis, distribution, regulation, and function remain controversial. Dinoflagellates are a major group of single-celled eukaryotic phytoplankton having peculiar crystalline chromosomes. Their genes are arranged in unidirectional gene clusters along the chromosomes and only have minimal transcriptional regulation, implying the involvement of other critical regulatory mechanisms in gene expression. Here, we found that m1A rather than m6A is the most prevalent mRNA modification in dinoflagellates and asymmetrically distributed along mature transcripts. Utilizing the dinoflagellate species Amphidinium carterae as a study model, we identified 13481 m1A peaks characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 10794 genes, many of which are involved in carbon and nitrogen metabolism. With enrichment around stop codon region and 3 UTR, dinoflagellate mRNA m1A exhibits negative correlation with translation efficiency. Notably, nitrogen depletion (N-depletion) treatment led to significant global decrease of mRNA m1A amount, causing dramatic variation in translation rates with minimal changes in transcription. Additionally, our analysis uncovered distinctive methylation patterns of m1A modification that appears to post-transcriptionally modulate gene expression through regulating translation efficiency. Thus, our findings provide the first comprehensive m1A map of dinoflagellate mRNA, shedding light on its crucial role as a post-transcriptional regulatory layer to compensate the degeneration of transcriptional regulation in dinoflagellate. This study also sets the stage for further investigation into the biogenesis and functional significance of mRNA m1A in eukaryotes.

Explore related subjects

molecular biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

LI, C., LI, Y., GUO, J., WANG, Y., SHI, X., ZHANG, Y., LIANG, N., YUAN, J., XU, J., Chen, H.. 2023-11-05. The highly abundant mRNA m1A modification: a new layer of gene regulation in dinoflagellates. https://doi.org/10.1101/2023.11.04.565600

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

LOca-1: A minimal calcium-activated arginyl-specific orthocaspase from the Loki's Castle hydrothermal vent field

Orthocaspases are prokaryotic homologs of metacaspases within the C14 family of cysteine proteases, yet their biochemical properties and cellular roles remain poorly understood. Here, we report the discovery and comprehensive characterization of LOca-1, a metagenome-derived orthocaspase from the Loki's Castle hydrothermal vent field. LOca-1 consists primarily of a single, conserved p20 catalytic domain and undergoes calcium-dependent activation through cleavage at a conserved arginine residue. Once activated, LOca-1 displays strict arginyl-specific proteolytic activity and strong selectivity for residues surrounding the cleavage site. The enzyme is both thermoactive and thermostable, exhibiting maximal activity at 65 {degrees}C and a melting temperature of approximately 72 {degrees}C. Structural modelling revealed conservation of the catalytic core relative to plant metacaspases despite substantial sequence divergence. To our knowledge, LOca-1 is only the second biochemically characterized orthocaspase and the first reported from a deep-sea hydrothermal vent environment. LOca-1 expands the known biochemical diversity of prokaryotic metacaspase homologs and provides insights into the properties of a minimal p20-domain orthocaspase. Together, our findings establish LOca-1 as a thermostable, calcium-activated arginyl-specific orthocaspase and provide a foundation for future studies of orthocaspase function in prokaryotes.

molecular biology↗
bioRxiv2026

A TMEM175 Mutation Disrupts the Lysosomal-Mitochondrial Axis Causing Short QT Syndrome and Sudden Cardiac Death

Short QT Syndrome (SQTS) is a rare cardiac channelopathy characterized by abnormally short QTc intervals and increased sudden cardiac death (SCD) risk. Only 20-30% of SQTS cases have been linked to genetic mutations, typi-cally in surface membrane ion channels. We identified a novel lysosomal TMEM175 gene mutation (p.Arg377His) in 7 patients in a family with SQTS and SCD. Genetic analyses, including whole exome sequencing in the family and rare-variant burden testing in [~]118,000 UK Biobank participants, sug-gested an association between TMEM175 rare variants and QT interval short-ening. Functional studies in CRISPR-engineered mice and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) revealed that TMEM175R377H causes shortened QT intervals and hastened repolariza-tion, respectively, as well an increased arrhythmia susceptibility. Isolated TMEM175R377H cardiomyocytes showed action potential duration (APD) abbre-viation, confirmed in whole TMEM175R377H mouse hearts and patient-specific iPSC-CM monolayers. In silico and electron microscopy studies showed that TMEM175R377H disrupts lysosomal-mitochondrial interactions, leading to mito-chondrial dysfunction, as evidenced by the reduced maximal respiration and spare respiratory capacity, with reduced ATP production, IKATP activation, and APD shortening. This mutation represents the first non-sarcolemmal ion chan-nel defect associated with SQTS and high SCD risk, potentially expanding the genetic landscape of the disease.

molecular biology↗
bioRxiv2026

Protecting host mitochondria with vitamin B3 preserves bioenergetics and thermogenesis during antibiotic treatment

Antibiotics that target bacterial translation can also impair mitochondrial function because mitochondria retain bacterial-like ribosomes. As antibiotic resistance continues to increase and the use of several broad-spectrum antibiotics has been limited by their mitochondrial toxicity, there is a growing need to understand their off-target effects in host physiology, and to identify strategies that can mitigate antibiotic-induced mitochondrial dysfunction. We demonstrate that antibiotic chloramphenicol (CA) induces a dose-dependent reduction in mitochondrial respiration and mitochondrial thermogenesis in Drosophila S2 cells, human HEK293T cells and in developing Drosophila larvae. In vivo, CA exposure triggers female-biased aberrant innate immune activation of hosts carrying naturally occurring mitochondrial rRNA variants. Metabolomic profiling revealed alterations in vitamin B3 metabolism in Drosophila during and following CA exposure. Among the vitamin B3 vitamers examined, nicotinamide (NAM) exhibited the strongest protective effect, mitigating the CA-induced impairments in mitochondrial respiration and thermogenesis, as well as aberrant immune activation. We identify mitochondrial thermogenesis as a previously unrecognized target of antibiotic-induced mitochondrial perturbation and a sensitive marker of mitochondrial stress. Furthermore, we demonstrate that co-supplementation of CA with NAM mitigates antibiotic-induced mitochondrial toxicity through evolutionarily conserved mitochondrial pathways. Finally, we establish Drosophila as a powerful model for investigating antibiotic-induced mitochondrial dysfunction and for developing therapeutic strategies to protect host mitochondria during antibiotic treatment.

molecular biology↗