bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.01.24.917260

Transcriptional analysis supports the expression of human snRNA variants and reveals U2 snRNA homeostasis by an abundant U2 variant

Kosmyna, B.·Gupta, V.·Query, C. C.
View original source ↗Export metadata ↓

Abstract

Although expansion of snRNA genes in the human genome and sequence variation in expressed transcripts were both identified long ago, no study has comprehensively analyzed which genes are transcriptionally active. Here, we use comprehensive bioinformatic analysis to differentiate between similar or identical genomic loci to determine that 49 snRNA genes are actively transcribed. This greatly expands on previous observation of sequence variation within snRNA transcripts. Further analysis of U2 snRNA variants reveals sequence variation maintains conserved secondary structures, yet sensitizes these U2 snRNAs to modulation of assembly factors. Homeostasis of total U2 snRNA level is maintained by altering the ratio of canonical and an abundant U2 snRNA variant. Both canonical and variant snRNA promoters respond to MYC and appear differentially sensitive to increased MYC levels. Thus, we identify transcribed snRNA variants and the sequence variation within, and propose mechanisms of transcriptional and post-transcriptional regulation of snRNA levels and pre-mRNA splicing. HIGHLIGHTSO_LIChIP-seq of active promoters identifies uncharacterized snRNA genes C_LIO_LITranscribed repetitive snRNA genes are distinguished from falsely-mapped snRNA loci C_LIO_LIU2 snRNA variants are sensitive to modulations in snRNP assembly C_LIO_LIWidely expressed U2 snRNA variants provide homeostasis for total U2 snRNP levels C_LI

Explore related subjects

molecular biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kosmyna, B., Gupta, V., Query, C. C.. 2020-01-25. Transcriptional analysis supports the expression of human snRNA variants and reveals U2 snRNA homeostasis by an abundant U2 variant. https://doi.org/10.1101/2020.01.24.917260

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

KEEP EXPLORING

Related preprints

bioRxiv2026

Fatty Acid Synthase Binds Cellular mRNAs and its Depletion Reduces Translational Efficiency

Metabolic enzymes with non-canonical RNA binding activity have drawn a growing interest, due to their implications for basic biology and disease. Here we present the first endogenous RNA interactome of fatty acid synthase (FASN), an emerging oncological and virological target. Utilizing crosslinking-based approaches, we characterize the direct RNA association of FASN in two human cell lines, identifying over 6000 binding sites across over 3500 protein-coding genes, with a striking preference for the 5' UTR. We provide a functional cross-screen on the effects of FASN depletion on cellular translation. This integration with ribosome profiling indicated a preferential reduction in the translational efficiencies of FASN-associated mRNAs - an effect shown to be dependent on binding location and site number. Associated transcripts were enriched for morphogenic and cell division-related functions, as well as palmitoylated proteins. This correlative work primes further investigation of FASN as a regulator of translation of its target mRNAs.

molecular biology↗
bioRxiv2026

Genomic features and instability of linezolid resistance in vancomycin-resistant Enterococcus faecalis ST525

This study investigated the mechanisms of oxazolidinone resistance and genomic background in clinical ST525 Enterococcus faecalis isolates, a poorly characterized lineage reported in Brazilian hospitals as either vancomycin-resistant (VRE) or linezolid- and vancomycin-resistant (LVRE). Five LVREfs from intensive care unit patients (linezolid MICs, 8-32 mg/L; vancomycin MICs, >256 mg/L) carried only G2576T and G2505A (in three of four rrl copies) as known linezolid resistance determinants, despite variable linezolid MICs. During serial in vitro passages without antibiotic pressure, isolates with initial MICs of 8-16 mg/L exhibited progressive MIC reductions accompanied by reversion of mutant to wild-type rrl copies, whereas the isolate with an initial MIC of 32 mg/L maintained high-level resistance without reversion. Additional domain V substitutions emerged during MIC decline, while growth kinetics remained broadly similar. Whole-genome sequencing of a representative isolate (LVREfs L7) revealed a ~2.8-Mb chromosome enriched in mobile genetic elements (~8.6%), lacking a functional CRISPR-Cas system. A plasmid-borne prototype Tn1546 carrying vanA, devoid of internal insertion sequences, was found inserted into a Tn3-family transposase gene, a platform not typically associated with vanA mobilization. Together, these findings indicate that ST525 LVREfs, whose genomic features are consistent with long-term persistence in hospitals, may pose a challenge to routine susceptibility testing. A single mutational mechanism can yield variable linezolid MICs, and the ratio of mutated vs wild-type rrl copies can become heterogeneous in the absence of antibiotic pressure, without correlating directly with these values, contrary to the well-documented copy number-MIC correlation.

molecular biology↗
bioRxiv2026

Global repression of mesenchymal genes in epithelial cells by the histone demethylase LSD1

Epithelial-mesenchymal transition (EMT) is an essential process in development, tissue repair, and tumour metastasis, and is triggered by SNAI, ZEB and TWIST transcription factors, that recruit lysine-specific demethylase 1 (LSD1) to repress epithelial genes such as E-cadherin. In mesenchymal cells, LSD1 inhibition restores E-cadherin expression and reduces migration and invasion, consistent with LSD1 inhibition reverting EMT, and offering a therapeutic modality for EMT-associated disease. Recent data, however, suggest context-dependent roles for LSD1, as its inhibition in epithelial cells increases mesenchymal marker expression, potentially promoting EMT. To investigate this discrepancy, we mapped genome-wide binding of LSD1 in HCT116 epithelial cells and used rapid degron-mediated ablation of endogenous LSD1 to measure changes in nascent and steady-state transcription and chromatin accessibility. In epithelial cells, LSD1 binds constitutively-accessible, primed mesenchymal promoters. These are rapidly derepressed after LSD1 ablation, with activation of SNAI2 and ZEB1, which repress epithelial hallmarks such as E-cadherin. Re-introduction of LSD1 downregulates SNAI2 and ZEB1 but, surprisingly, further represses E-cadherin, indicating sustained loss of epithelial characteristics. Collectively, our results show that LSD1 maintains epithelial identity by repressing mesenchymal genes, questioning the therapeutic utility of LSD1 inhibition for EMT control.

molecular biology↗