Probing enzyme-dependent pseudouridylation using direct RNA sequencing to assess neuronal epitranscriptome plasticity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

Chemical modifications in mRNAs such as pseudouridine (psi) can regulate gene expression, although our understanding of the functional impact individual psi modifications, especially neuronal cells, is limited. We apply nanopore direct RNA sequencing to investigate dynamics under cellular perturbations SH-SY5Y cells. assign sites synthases using siRNA-based knockdown. A steady-state enzyme-substrate model reveals a strong correlation between synthase and mRNA substrate levels modification frequencies. Next, we performed either differentiation or lead-exposure cells found that, upon lead exposure, not differentiation, frequency less dependent on enzyme suggesting translational control. Finally, compared plasticity across states that plastic be condition-dependent condition-independent; several these fall within transcripts encoding proteins involved processes. Our analysis validation enable investigations into modifications.

Language: Английский

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Transposable elements contribute to the spatiotemporal microRNA landscape in human brain development

RNA, Journal Year: 2022, Volume and Issue: 28(9), P. 1157 - 1171

Published: June 22, 2022

Transposable elements (TEs) contribute to the evolution of gene regulatory networks and are dynamically expressed throughout human brain development disease. One mechanism influenced by TEs is miRNA system post-transcriptional control. sequences frequently overlap TE loci this expression landscape crucial for control in adult different cellular contexts. Despite this, a thorough investigation spatiotemporal TE-embedded miRNAs lacking. Here, we identify spatiotemporally dynamic between childhood adolescent stages development. These sometimes arise from two apposed same subfamily, such as L2 or MIR elements, but majority cases stem solo TEs. They give rise silico predicted high-confidence pre-miRNA hairpin structures, likely represent functional miRNAs, have genic targets associated with neurogenesis. distinct cerebellum when compared other regions, has previously been described expression. Furthermore, detect nonannotated development, suggestive undetected network. Together, non-TE-embedded networks, implications which constitute extensive avenues future experimental research. To facilitate interactive exploration these dynamics, provide “Brain miRTExplorer” web application freely accessible community.

Language: Английский

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Species-specific rewiring of definitive endoderm developmental gene activation via endogenous retroviruses through TET1-mediated demethylation

Cell Reports, Journal Year: 2022, Volume and Issue: 41(11), P. 111791 - 111791

Published: Dec. 1, 2022

Transposable elements (TEs) are the major sources of lineage-specific genomic innovation and comprise nearly half human genome, but most their functions remain unclear. Here, we identify that a series endogenous retroviruses (ERVs), TE subclass, regulate transcriptome at definitive endoderm stage with in vitro differentiation model from embryonic stem cell. Notably, these ERVs perform as enhancers containing binding sites for critical transcription factors lineage specification. Genome-wide methylation analysis shows derepressed by TET1-mediated DNA demethylation. LTR6B, representative activating ERV, contains FOXA2 GATA4 governs primate-specific expression its neighboring developmental genes such ERBB4 endoderm. Together, our study proposes evidence recently evolved represent potent de novo regulatory elements, which, turn, fine-tune species-specific transcriptomes during development.

Language: Английский

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Transposon control as a checkpoint for tissue regeneration

Development, Journal Year: 2022, Volume and Issue: 149(22)

Published: Nov. 15, 2022

ABSTRACT Tissue regeneration requires precise temporal control of cellular processes such as inflammatory signaling, chromatin remodeling and proliferation. The combination these forms a unique microenvironment permissive to the expression, potential mobilization of, transposable elements (TEs). Here, we develop hypothesis that TE activation creates barrier tissue repair must be overcome achieve successful regeneration. We discuss how uncontrolled activity may impede restoration review mechanisms by which controlled during posit diversification co-evolution TEs host contribute wide variation in regenerative competency across tissues species.

Language: Английский

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Epigenetics and substance use disorders: translational aspects

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 353 - 378

Published: Jan. 1, 2024

Language: Английский

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