Biology subjects

Van Treeck, B.

Publications and source records attributed to Van Treeck, B..

4 recordsLinked to original sources

bioRxiv2025

Lineage-Specific Evolution, Structural Diversity, and Activity of R2 Retrotransposons in Animals

Retrotransposons play outsized roles in the evolution of gene regulation, genome function, and disease pathogenesis and more recently, have sparked interest as workhorses for new gene therapy approaches. R2 retrotransposons insert site-specifically to the multicopy genes encoding 28S ribosomal RNA at a target sequence conserved broadly across eukaryotic evolution. R2 retrotransposons have been detected in many animals, but previous surveys have been limited in scope and methodology. Here, we substantially expand the known distribution of R2 retrotransposons from previously unrepresented or underrepresented taxonomic groups ranging from ctenophores to amphibians and reptiles. We discover diverse R2 domain architectures and motifs and identify many new avian R2 candidates for genome engineering development. Overall, phylogenetic analyses reveal two highly successful R2 lineages. We observe properties of each lineage in several features of the domains that mediate DNA recognition and in co-evolving signatures within the reverse transcriptase domain. Within each of the two lineages, R2 protein sequences do not necessarily preserve the unifying configuration of N-terminal DNA-binding domains implied in the current clade classification scheme. We show that recombinant R2 proteins with distinctive domain architectures and distribution across major animal classes support target-primed reverse transcription with conserved site specificity. Our analysis of the surprisingly varied domain architectures that support target-site specificity informs new R2 classification criteria and provides a greatly expanded foundation for additional structure/function insights about DNA binding selectivity. This expanded perspective on R2 evolution informs approaches for engineering therapeutic gene insertion technologies and offers an opportunity to investigate the conservation and diversification of retrotransposons.

evolutionary biology↗

bioRxiv2020

RNA partitioning into stress granules is based on the summation of multiple interactions

Stress granules (SGs) are stress-induced RNA-protein assemblies formed from a complex transcriptome of untranslating ribonucleoproteins (RNPs). Although RNAs can be either enriched or depleted from SGs, the rules that dictate RNA partitioning into SGs are unknown. We demonstrate that the SG-enriched NORAD RNA is sufficient to enrich a reporter RNA within SGs through the combined effects of multiple elements. Moreover, artificial tethering of G3BP1 or TIA1 can target mRNAs into SGs in a dose-dependent manner that suggests individual protein interactions have small effects on the SG partitioning of mRNPs, which is supported by the observation that the SG transcriptome is largely unchanged in cell lines lacking the abundant SG RNA-binding proteins G3BP1 and G3BP2. We suggest the targeting of RNPs into SGs is due to a summation of potential RNA-protein, protein-protein, and RNA-RNA interactions with no single interaction dominating RNP recruitment into SGs.

molecular biology↗

bioRxiv2019

Modulation of RNA condensation by the eIF4A RNA helicase

Stress granules are condensates of non-translating mRNAs and proteins involved in the stress response and neurodegenerative diseases. Stress granules form in part through intermolecular RNA-RNA interactions, although the process of RNA condensation is poorly understood. In vitro, we demonstrate that RNA is effectively recruited to the surfaces of RNA or RNP condensates. We demonstrate that the DEAD-box protein eIF4A reduces RNA condensation in vitro and limits stress granule formation in cells. This defines a purpose for eIF4A to limit intermolecular RNA-RNA interactions in cells, thereby allowing for proper RNP function. These results establish an important role for DEAD-box proteins as ATP-dependent RNA chaperones that can limit the intermolecular condensation and entanglement of RNA, analogous to the function of proteins like HSP70 in combatting protein aggregates. eTOC BlurbStress granules are formed in part by the process of RNA condensation, which is mediated by and promotes trans RNA-RNA interactions. The essential DEAD-box protein and translation initiation factor eIF4A limits stress granule formation by reducing RNA condensation through its function as an ATP-dependent RNA binding protein, behaving analogously to how protein chaperones like HSP70 combat protein aggregates. HighlightsO_LIRNA condensates promote intermolecular RNA-RNA interactions at their surfaces C_LIO_LIeIF4A limits the recruitment of RNAs to stress granules in cells C_LIO_LIeIF4A reduces the nucleation of stress granules in cells C_LIO_LIRecombinant eIF4A1 inhibits the condensation of RNA in vitro in an ATP-dependent manner C_LI

biochemistry↗

bioRxiv2017

Intrinsically disordered regions contribute promiscuous interactions to RNP granule assembly

Eukaryotic cells contain large RNA-protein assemblies referred to as RNP granules, whose assembly is promoted by both traditional protein interactions and intrinsically disordered protein domains. Using RNP granules as an example, we provide evidence for an assembly mechanism of large cellular structures wherein specific protein-protein or protein-RNA interactions act together with promiscuous interactions of intrinsically disordered regions (IDRs). This synergistic assembly mechanism illuminates RNP granule assembly, and explains why many components of RNP granules, and other large dynamic assemblies, contain IDRs linked to specific protein-protein or protein-RNA interaction modules. We suggest assemblies based on combinations of specific interactions and promiscuous IDRs are common features of eukaryotic cells.

biochemistry↗