Background: MicroRNA isoforms (isomiRs), tRNA-derived fragments (tRFs), and rRNA-derived fragments (rRFs) represent most of the small non-coding RNAs (sncRNAs) found in cells. Members of these three classes modulate messenger RNA (mRNA) and protein abundance and are dysregulated in diseases. Experimental studies to date have assumed that the subcellular distribution of these molecules is well-understood, independent of cell type, and the same for all isoforms of a sncRNA.
Results: We tested these assumptions by investigating the subcellular distribution of isomiRs, tRFs, and rRFs in biological replicates from three cell lines from the same tissue and same-sex donors that model the same cancer subtype. In each cell line, we profiled the isomiRs, tRFs, and rRFs in the nucleus, cytoplasm, whole mitochondrion (MT), mitoplast (MP), and whole cell. Using a rigorous mathematical model we developed, we accounted for cross-fraction contamination and technical errors and adjusted the measured abundances accordingly. Analyses of the adjusted abundances show that isomiRs, tRFs, and rRFs exhibit complex patterns of subcellular distributions. These patterns depend on each sncRNA's exact sequence and the cell type. Even in the same cell line, isoforms of the same sncRNA whose sequences differ by a few nucleotides (nts) can have different subcellular distributions.
Conclusions: SncRNAs with similar sequences have different subcellular distributions within and across cell lines, suggesting that each isoform could have a different function. Future computational and experimental studies of isomiRs, tRFs, and rRFs will need to distinguish among each molecule's various isoforms and account for differences in each isoform's subcellular distribution in the cell line at hand. While the findings add to a growing body of evidence that isomiRs, tRFs, rRFs, tRNAs, and rRNAs follow complex intracellular trafficking rules, further investigation is needed to exclude alternative explanations for the observed subcellular distribution of sncRNAs.
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http://dx.doi.org/10.1186/s12915-024-01970-6 | DOI Listing |
EMBO J
January 2025
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Biogenesis of membrane-bound organelles involves the synthesis, remodeling, and degradation of their constituent phospholipids. How these pathways regulate organelle size remains poorly understood. Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Methodological developments in biomedical research are currently moving towards single-cell approaches. This allows for a much better spatial and functional characterization of, for example, the deterioration of cells within a tissue in response to noxae. However, subcellular resolution is also essential to elucidate whether observed impairments are driven by an explicit organelle.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Institute of Optical Materials and Chemical Biology, Guangxi Key Laboratory of Electrochemical Energy Materials, School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, People's Republic of China.
Monitoring subcellular organelle dynamics in real time and precisely assessing membrane heterogeneity in living cells are very important for studying fundamental biological mechanisms and gaining a comprehensive understanding of cellular processes. However, there remains a shortage of effective tools for these purposes. Herein, we propose a strategy to develop the exchangeable water-sensing probeAPBD for time-lapse imaging of dynamics in cellular membrane-bound organelle morphology with structured illumination microscopy at the nanoscale.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Homi Bhabha National Institute, Mumbai, Maharashtra, India.
Background: Recent advances in understanding the regulatory networks implicated in Alzheimer's Disease (AD) evinces the involvement of long non-coding RNAs (lncRNAs) as crucial regulatory players. The present study explores the role played by maternally imprinted lncRNA XIST in regulating the sex-biased prevalence of AD.
Method: With whole transcriptomic sequencing data from the hippocampal RNA of post-mortem AD brains from humans and APP/PS1 mice, the altered expression of XIST in AD was studied.
Alzheimers Dement
December 2024
Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom.
Background: Knowledge of the chemical composition of amyloid plaques and tau tangles at the earlier stages of Alzheimer's disease (AD) pathology is sparse. This is due to limited access to human brain during life and at the earlier stages of AD pathophysiology and technical limitations in quantifying amyloid and tau species at a subcellular level. Understanding the chemical composition of plaques and tangles, how rapidly they grow and what factors drive growth is important for developing and refining therapeutics.
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