Biology subjects

Lenz, E.

Publications and source records attributed to Lenz, E..

3 recordsLinked to original sources

bioRxiv2026

Profiling and Targeting of Regulatory RNAs to Upregulate Gene Expression

Transcription of long noncoding RNAs (lncRNAs), including enhancer RNAs (eRNAs) and promoter-associated RNAs (paRNAs), collectively termed regulatory RNAs (regRNAs), is a hallmark of active gene expression, yet it remains unknown whether regRNAs can be targeted to selectively enhance transcription in cis. We developed regRNA Capture-seq, a high-throughput method to profile regRNAs, and applied it to primary human hepatocytes, annotating thousands of regRNAs at [~]2,000 enhancers and promoters. Using this approach, we interrogated a genetically validated enhancer of the ornithine transcarbamylase (OTC) gene, mutations of which cause OTC deficiency (OTCD), the most common urea cycle disorder. Antisense oligonucleotides (ASOs) targeting enhancer-derived regRNAs led to dose-dependent upregulation of OTC in hepatocytes. Mechanistically, ASOs altered regRNA structure, elevated regRNA levels, displaced transcriptional repressors, and increased H3K27 acetylation at the targeted enhancer. This work establishes a potential therapeutic strategy for addressing haploinsufficiency and highlights regRNAs as actionable targets for ASO-mediated upregulation of gene expression.

genomics↗

bioRxiv2024

Coral long-term recovery after bleaching: implications for sexual reproduction and physiology.

This study examined the long-term impacts of coral bleaching on the reproduction and physiology of Montipora capitata, a dominant reef-building coral in Hawaii. We monitored bleached and non-bleached colonies during and after a natural coral bleaching event in 2014 and analyzed reproductive traits and transcriptomic signatures eight months later. Our study shows that non-bleached and bleached colonies successfully produced gametes. Colonies that bleached had smaller oocytes, and development was slower than in colonies that did not bleach. Corals with different vulnerabilities to bleaching exhibited distinct transcriptomic responses eight months after a bleaching event. Those more prone to bleaching showed suppression of transcripts associated with sperm motility, calcification, and immunity. We found distinct transcriptomic signatures between fringing and patch reefs, suggesting local adaptation and/or acclimatization. To conserve coral reefs and better understand how they will be affected by future heat stress, we need to track which colonies survive and examine how their physiological and reproductive processes are impacted in the short- and long-term. This is critical as consecutive bleaching events become more frequent, and corals have less time to recover. Our study provides valuable molecular and reproductive data that can be used for conservation and management purposes. This information can help us identify signs of coral vulnerability and resilience to bleaching, project how future bleaching events will affect coral reproduction, determine which traits are most at risk, and assess which sites are more likely to be compromised.

physiology↗

bioRxiv2023

Parental effects provide an opportunity for coral resilience following major bleaching events

Identifying processes that promote coral reef recovery and resilience is crucial as ocean warming becomes more frequent and severe. Sexual reproduction is essential for the replenishment of coral populations and maintenance of genetic diversity; however, the ability for corals to reproduce may be impaired by marine heatwaves that cause coral bleaching. In 2014 and 2015, the Hawaiian Islands experienced coral bleaching with differential bleaching susceptibility in the species Montipora capitata, a dominant reef-building coral in the region. We tested the hypothesis that coral bleaching resistance enhances reproductive capacity and offspring performance by examining the reproductive biology of colonies that bleached and recovered (B) and colonies that did not bleach (NB) in 2015 in the subsequent spawning seasons. The proportion of colonies that spawned was higher in 2016 than in 2017. Regardless of parental bleaching history, we found eggs with higher abnormality and bundles with fewer eggs in 2016 than 2017. While reproductive output was similar between B and NB colonies in 2016, survivorship of offspring that year were significantly influenced by the parental bleaching history (egg donor x sperm donor: B x B, B x NB, NB x B, and NB x NB). Offspring produced by NB egg donors had the highest survivorship, while offspring from previously bleached colonies had the lowest survivorship, highlighting the negative effects of bleaching on parental investment and offspring performance. While sexual reproduction continues in M. capitata post-bleaching, gametes are differentially impacted by recovery time following a bleaching event and by parental bleaching resistance. Our results demonstrate the importance of identifying bleaching resistant individuals during and after heating events. This study further highlights the significance of maternal effects through potential egg provisioning for offspring survivorship and provides a baseline for human-assisted intervention (i.e., selective breeding) to mitigate the effects of climate change on coral reefs.

zoology↗