Biology subjects

Gabel, A.

Publications and source records attributed to Gabel, A..

5 recordsLinked to original sources

bioRxiv2024

Comprehensive annotations of alternative splicing, lncRNAs, and circRNAs in seven species of flowering plants

The successful occupation of terrestrial habitats by early plants was catalyzed by the adaptive evolution of new organs able to supply water and compensate for the gravitational impact under changing land conditions. Because plants are sessile, it has been proposed that the capacity of plants to innovate specialized organs is driven by a complex interplay between developmental gene expression and regulatory RNAs such as lncRNAs and circRNAs, evolving through sequence polymorphisms, genomic rearrangements, and expression divergence. Despite the importance of alternative and noncoding transcripts for enabling plant life, their accurate quantification causes major challenges as many of them are expressed at low levels and tissue-specific. Here, we describe the re-annotation of seven land plant genomes based on deep, organ-specific, ribo-depleted developmental RNA-Seq data. Using this comparative resource, we uncover 5,000 new lncRNAs and 2,000 new circular RNAs that are promising candidates for further functional investigation. Our annotation will become a reference catalog for studies on plant organ evolution and for uncovering tissue-specific patterns of transcript emergence.

plant biology↗

bioRxiv2024

Rapid evolution of gene expression patterns in flowering plants

Phenotypic differences between species are largely driven by changes in both protein-coding sequence and gene expression 1. The evolutionary history of angiosperms (flowering plants) is characterised by a highly accelerated rate of diversification, which Darwin referred to as an "abominable mystery" 2. Here we show, by analysing the transcriptomes from eight organs across seven species, that angiosperm protein-coding gene expression patterns evolve rapidly: within 45 million years, expression levels of orthologous genes diverged so strongly that they are more similar between different organs within a species than between what are considered homologous organs from different species. This finding differs from previous observations in mammals, which demonstrated that organ-dependent gene expression levels are largely conserved 3, 4, 5. Among the angiosperm organs, meristems and leaves show the highest degree of expression conservation, whereas stamen and pollen transcriptomes diverge rapidly. Examining changes in the expression level of functionally related genes, we found low rates for those involved in key cellular, metabolic and developmental processes. In contrast, particularly high rates were observed for genes that are involved in the response to endogenous and external stimuli, presumably reflecting an adaptive response of flowering plants to ever-changing environments. Our work reveals that the evolution of gene expression progresses at different rates in angiosperms and mammals, and provides a comprehensive resource to perform cross-kingdom comparative studies of transcriptome evolution.

plant biology↗

bioRxiv2023

SHIFTR enables the unbiased and multiplexed identification of proteins bound to specific RNA regions in live cells

RNA-protein interactions determine the cellular fate of RNA and are central to regulating gene expression outcomes in health and disease. To date, no method exists that is able to identify proteins that interact with specific regions within endogenous RNAs in live cells. Here, we develop SHIFTR (Selective RNase H-mediated interactome framing for target RNA regions), an efficient and scalable approach to identify proteins bound to selected regions within endogenous RNAs using mass spectrometry. Compared to state-of-the-art techniques, SHIFTR is superior in accuracy, captures close to zero background interactions and requires orders of magnitude lower input material. We establish SHIFTR workflows for targeting RNA classes of different length and abundance, including short and long non-coding RNAs, as well as mRNAs and demonstrate that SHIFTR is compatible with sequentially mapping interactomes for multiple target RNAs in a single experiment. Using SHIFTR, we comprehensively identify interactions of cis-regulatory elements located at the 5' and 3'- terminal regions of the authentic SARS-CoV-2 RNA genome in infected cells and accurately recover known and novel interactions linked to the function of these viral RNA elements. SHIFTR enables the systematic mapping of region-resolved RNA interactomes for any RNA in any cell type and has the potential to revolutionize our understanding of transcriptomes and their regulation.

molecular biology↗

bioRxiv2020

Discovery of synthetic lethal and tumor suppressive paralog pairs in the human genome

CRISPR knockout screens have accelerated the discovery of important cancer genetic dependencies. However, traditional CRISPR-Cas9 screens are limited in their ability to assay the function of redundant or duplicated genes. Paralogs in multi-gene families constitute two-thirds of the protein-coding genome, so this blind spot is the rule, not the exception. To overcome the limitations of single gene CRISPR knockout screens, we developed paired guide RNAs for Paralog gENetic interaction mapping (pgPEN), a pooled CRISPR/Cas9 approach which targets over a thousand duplicated human paralogs in single knockout and double knockout configurations. We applied pgPEN to two cell lineages and discovered that over 10% of human paralogs exhibit synthetic lethality in at least one cellular context. We recovered known synthetic lethal paralogs such as MAP2K1/MAP2K2, important drug targets such as CDK4/CDK6, and numerous other synthetic lethal pairs such as CCNL1/CCNL2. In addition, we identified ten tumor suppressive paralog pairs whose compound loss promotes cell growth. These findings identify a large number of previously unidentified essential gene families and nominate new druggable targets for oncology drug discovery. HighlightsO_LIComprehensive genetic interaction mapping of 1,030 human duplicated paralogs using a dual targeting CRISPR/Cas9 approach C_LIO_LIDuplicated paralogs are highly enriched for genetic interactions C_LIO_LISynthetic lethal paralogs include CCNL1/CCNL2, CDK4/CDK6, and GSK3A/GSK3B C_LIO_LITumor suppressor paralog pairs include CDKN2A/CDKN2B and FBXO25/FBXO32 C_LI

genomics↗

bioRxiv2017

Gene expression dynamics and inter-tissue recognition mechanisms during tissue fusion at the Arabidopsis graft junction

The ability for cut tissues to join together and form a chimeric organism is a remarkable property of many plants, however, grafting is poorly characterized at the molecular level. To better understand this process we monitored genome-wide temporal and spatial gene expression changes in grafted Arabidopsis thaliana hypocotyls. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than the other. This asymmetry correlated with sugar responsive genes and we observed an accumulation of starch above the graft that decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues indicating that a recognition mechanism activated that was independent of functional vascular connections. Auxin which is transported cell-to-cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes were expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, inter-tissue communication and tissue fusion events.

plant biology↗