Biology subjects

Houserova, D.

Publications and source records attributed to Houserova, D..

3 recordsLinked to original sources

bioRxiv2021

MicroRNA-like snoRNA-derived RNAs (sdRNAs) promote castration resistant prostate cancer

We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24 respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks 2nd in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.

cancer biology↗

bioRxiv2021

Salmonella Outer Membrane Vesicles contain tRNA Fragments (tRFs) that Inhibit Bacteriophage P22 infection

Salmonella Outer Membrane Vesicles (OMVs) were recently shown to inhibit P22 bacteriophage infection. Furthermore, despite there being several published reports now independently describing (1) the marked prevalence of tRFs within secreted vesicle transcriptomes and (2) roles for specific tRFs in facilitating/inhibiting viral replication, there have been no examinations of the effects of vesicle-secreted tRFs on viral infection reported to date. Notably, while specific tRFs have been reported in a number of bacteria, the tRFs expressed by salmonellae have not been previously characterized. As such, we recently screened small RNA-seq datasets for the presence of recurrent, specifically excised tRFs and identified 31 recurrent, relatively abundant tRFs expressed by Salmonella enterica serovar Typhimurium (SL1344). Whats more, we find S. Typhimurium OMVs contain significant levels of tRFs highly complementary to known Salmonella enterica-infecting bacteriophage with 17 of 31 tRFs bearing marked complementarity to at least one known Salmonella enterica-infecting phage (averaging 97.4% complementarity over 22.9 nt). Most notably, tRNA-Thr-CGT-1-1, 44-73, bears 100% sequence complementary over its entire 30 nt length to 29 distinct, annotated Salmonella enterica-infecting bacteriophage including P22. Importantly, we find inhibiting this tRF in secreted OMVs improves P22 infectivity in a dose dependent manner whereas raising OMV tRF levels conversely inhibits P22 infectivity. Furthermore, we find P22 phage pre-incubation with OMVs isolated from naive, control SL1344 S. Typhimurium, successfully rescues the ability of S. Typhimurium transformed with a specific tRNA-Thr-CGT-1-1, 44-73 tRF inhibitor to defend against P22. Collectively, these experiments confirm tRFs secreted in S. Typhimurium OMVs are directly involved with and required for the ability of OMVs to defend against bacteriophage predation. As we find the majority of OMV tRFs are highly complementary to an array of known Salmonella enterica-infecting bacteriophage, we suggest OMV tRFs may primarily function as a broadly acting, previously uncharacterized innate antiviral defense.

microbiology↗

bioRxiv2021

SALTS: SURFR (small noncoding RNA) And LAGOOn (long noncoding RNA) Transcriptomics Suite

The widespread utilization of high-throughput sequencing technologies has unequivocally demonstrated that eukaryotic transcriptomes consist primarily (>98%) of non-coding RNA (ncRNA) transcripts significantly more diverse than their protein-coding counterparts. ncRNAs are typically divided into two categories based on their length. (1) ncRNAs less than 200 nucleotides (nt) long are referred as small non-coding RNAs (sncRNAs) and include microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transfer ribonucleic RNAs (tRNAs), etc., and the majority of these are thought to function primarily in controlling gene expression. That said, the full repertoire of sncRNAs remains fairly poorly defined as evidenced by two entirely new classes of sncRNAs only recently being reported, i.e., snoRNA-derived RNAs (sdRNAs) and tRNA-derived fragments (tRFs). (2) ncRNAs longer than 200 nt long are known as long ncRNAs (lncRNAs). lncRNAs represent the 2nd largest transcriptional output of the cell (behind only ribosomal RNAs), and although functional roles for several lncRNAs have been reported, most lncRNAs remain largely uncharacterized due to a lack of predictive tools aimed at guiding functional characterizations. Importantly, whereas the cost of high-throughput transcriptome sequencing is now feasible for most active research programs, tools necessary for the interpretation of these sequencings typically require significant computational expertise and resources markedly hindering widespread utilization of these datasets. In light of this, we have developed a powerful new ncRNA transcriptomics suite, SALTS, which is highly accurate, markedly efficient, and extremely user-friendly. SALTS stands for SURFR (sncRNA) And LAGOOn (lncRNA) Transcriptomics Suite and offers platforms for comprehensive sncRNA and lncRNA profiling and discovery, ncRNA functional prediction, and the identification of significant differential expressions among datasets. Notably, SALTS is accessed through an intuitive Web-based interface, can be used to analyze either user-generated, standard next-generation sequencing (NGS) output file uploads (e.g., FASTQ) or existing NCBI Sequence Read Archive (SRA) data, and requires absolutely no dataset pre-processing or knowledge of library adapters/oligonucleotides. SALTS constitutes the first publically available, Web-based, comprehensive ncRNA transcriptomic NGS analysis platform designed specifically for users with no computational background, providing a much needed, powerful new resource capable of enabling more widespread ncRNA transcriptomic analyses. The SALTS WebServer is freely available online at http://salts.soc.southalabama.edu.

bioinformatics↗