bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.02.10.430566

The lncRNA EPB41L4A-AS1 regulates gene expression in the nucleus and exerts cell type-dependent effects on cell cycle progression

Samdal, H.·Hegre, S. A.·Chawla, K.·Liabakk, N.-B.·Aas, P. A.·Sporsheim, B.·Saetrom, P.
View original source ↗Export metadata ↓

Abstract

The long non-coding RNA (lncRNA) EPB41L4A-AS1 is aberrantly expressed in various cancers and has been reported to be involved in metabolic reprogramming and as a repressor of the Warburg effect. Although the biological relevance of EPB41L4A-AS1 is evident, its functional role seems to vary depending on cell type and state of disease. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we previously identified EPB41L4A-AS1 to be one of 59 lncRNAs with potential cell cycle functions. Here, we demonstrate that EPB41L4A-AS1 exists as bright foci and regulates gene expression in the nucleus in both cis and trans. Specifically, we find that EPB41L4A-AS1 positively regulates its sense overlapping gene EPB41L4A and influences expression of hundreds of other genes, including genes involved in cell proliferation. Finally, we show that EPB41L4A-AS1 affects cell cycle phase distribution, though these effects vary between cell types.

Explore related subjects

molecular biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Samdal, H., Hegre, S. A., Chawla, K., Liabakk, N.-B., Aas, P. A., Sporsheim, B., Saetrom, P.. 2021-02-10. The lncRNA EPB41L4A-AS1 regulates gene expression in the nucleus and exerts cell type-dependent effects on cell cycle progression. https://doi.org/10.1101/2021.02.10.430566

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

KEEP EXPLORING

Related preprints

bioRxiv2026

A G-Quadruplex Containing First Intron Harbors a Functional Polyadenylation Signal in TP53

First introns of mammalian genes are often longer than other introns and may contain regulatory elements, suggesting that they may have roles in gene regulation. We detected a previously unannotated, low abundance intronic transcript, TP53-INT1, using long-read direct RNA sequencing data. TP53-INT1 has low coding potential and terminates within the first and longest intron of TP53. The transcript structure and 3'-end were validated by independent experimental and in silico evidence. We identified a canonical polyadenylation signal upstream of the transcript termination site and demonstrated its functionality using reporter assays. Furthermore, a potential G-quadruplex (G4)-forming sequence was identified upstream of this polyadenylation signal. The G4-forming potential was confirmed using spectroscopic and thermal stability analyses. Complementing the in vitro characterizations, treatment with Pyridostatin, a G4-stabilizing drug, was associated with decreased TP53 expression. Together, these findings characterize a previously unannotated TP53 intronic transcript and reveal a local genomic context combining accessible chromatin, a functional polyadenylation signal, and a potential G4-forming sequence that may influence full-length transcription.

molecular biology↗
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↗