Biology subjects

Grote, S.

Publications and source records attributed to Grote, S..

4 recordsLinked to original sources

bioRxiv2024

SEISMICgraph: a web-based tool for RNA structure data visualization

In recent years, RNA has been increasingly recognized for its essential roles in biology, functioning not only as a carrier of genetic information but also as a dynamic regulator of gene expression through its interactions with other RNAs, proteins, and itself. Advances in chemical probing techniques have significantly enhanced our ability to identify RNA secondary structures and understand their regulatory roles. These developments, alongside improvements in experimental design and data processing, have greatly increased the resolution and throughput of structural analyses. Here, we introduce SEISMICgraph, a web-based tool designed to support RNA structure research by offering data visualization and analysis capabilities for a variety of chemical probing modalities. SEISMICgraph enables simultaneous comparison of data across different sequences and experimental conditions through a user-friendly interface that requires no programming expertise. We demonstrate its utility by investigating known and putative riboswitches and exploring how RNA modifications influence their structure and binding. SEISMICgraphs ability to rapidly visualize adenine-dependent structural changes and assess the impact of pseudouridylation on these transitions provides novel insights and establishes a roadmap for numerous future applications. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/615187v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1fac718org.highwire.dtl.DTLVardef@1252f03org.highwire.dtl.DTLVardef@31968dorg.highwire.dtl.DTLVardef@1930c4f_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

Developmental editing control of mRNA ND7 involves KREH2 helicase-dependent gRNAselection and proposed RNA structure in Trypanosoma brucei

Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical "terminator" gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a "moonlighting" gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2s novel dual role tunes mitochondrial gene expression in either direction during development.

molecular biology↗

bioRxiv2023

Structure of pre-miR-31 reveals an active role in Dicer processing

As an essential post-transcriptional regulator of gene expression, microRNA (miR) levels must be strictly maintained. The biogenesis of many, but not all, miRs is mediated by trans-acting protein partners through a variety of mechanisms, including remodeling of the RNA structure. miR-31 functions as an oncogene in numerous cancers and interestingly, its biogenesis is not known to be regulated by protein binding partners. Therefore, the intrinsic structural properties of pre-miR-31 can provide a mechanism by which its biogenesis is regulated. We determined the solution structure of the precursor element of miR-31 (pre-miR-31) to investigate the role of distinct structural elements in regulating Dicer processing. We found that the presence or absence of mismatches within the helical stem do not strongly influence Dicer processing of the pre-miR. However, both the apical loop size and structure at the Dicing site are key elements for discrimination by Dicer. Interestingly, our NMR-derived structure reveals the presence of a triplet of base pairs that link the Dicer cleavage site and the apical loop. Mutational analysis in this region suggests that the stability of the junction region strongly influence both Dicer binding and processing. Our results enrich our understanding of the active role that RNA structure plays in regulating Dicer processing which has direct implications for control of gene expression.

biophysics↗

bioRxiv2020

A high-coverage Neandertal genome from Chagyrskaya Cave

We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We estimate that this individual lived ~80,000 years ago and was more closely related to Neandertals in western Eurasia (1,2) than to Neandertals who lived earlier in Denisova Cave (3), which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a first view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.

genomics↗