Dr. Jinwei Zhang, Ph.D., generously agreed to host Liz as a visiting researcher for two weeks in his lab at the National Institutes of Health (NIH), Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). During this brief stay, Liz was able to tour multiple facilities at the NIH, network with postdoctoral scientists from around the world, and receive expert advice and assistance on her research. The Zhang lab excels in RNA structure determination by x-ray crystallography and has solved multiple structures using de-novo anomalous phasing. Dr. Zhang and his postdoctoral researchers, Dr. Charles Bou-Nader, Dr. Krishna Sapkota, Dr. Ilias Skeparnias, and Dr. Aline Umuhire Juru, worked with Liz to create a molecular replacement model by systematic refinement of fragment search models. As well as the molecular replacement assistance, they suggested many methods to improve the diffraction data Liz collect for phasing with heavy atoms, like iridium hexamine chloride. Overall, the experience improved her chance of solving the structure of her RNA of interest and allowed her to experience, briefly, what it would be like to work at a government research institute.

Learn more about the RNA Society Sponsored Research Scholar Exchange Program

RNA Collaborative - Live Chat with Lighting Talk Competition Awardees

The RiboClub Annual Meeting aims at encouraging the exchange of ideas and stimulates collaborations between RNA biologists around the world. The meeting covers different topics related to the chemistry, structure and biology of RNA with emphasis on upcoming and debatable biological questions.

September 18 – 22, 2022

Quebec, Canada

The symposium aims to highlight success stories from the drug discovery community at Michigan, share best practices, and provide opportunities for networking. A poster session for graduate students and trainees will occur midday.

Mon, Sep 21, 2022

9:00 a.m. - 4:00 p.m.

The Inaugural Brain Cancer Symposium brings together experts from around the world in a weekend full of talks, posters, and social events.

Sep 30 – Oct 1, 2022

Ann Arbor, MI

The Midwest Symposium on Oligonucleotide Therapeutics is a grassroots meeting in Indianapolis supported by an Oligonucleotide Therapeutics Society (OTS) Local Delivery Grant.

October 8 – 9, 2022

Indianapolis, IN

Co-sponsored by Neurology, Human Genetics and the Center for RNA Biomedicine

Mon, Oct 10, 2022

6:30 - 9:00 p.m.

Michigan Theatre

Ann Arbor, MI

The symposium will feature world-class speakers, talks from submitted abstracts, and many great opportunities for networking. Abstract deadlines are Sept 16th (to be considered for talks) and Sept 26th for posters.

October 13–14, 2022

Durham, NC

The Rustbelt is in-person and excited to offer Presentations, Workshops, Awards, and more!

October 14–15, 2022

Cleveland OH

Our members' publications are available through Altmetrics. Queries are currently available: CRISPR, microRNA, molecule, RNA, RNA therapeutics, transcriptome, and translation. Below are recent highlights.

Ljungman M. (2022). Transcription and genome integrity. DNA repair, 118, 103373. Advance online publication. https://doi.org/10.1016/j.dnarep.2022.103373

Abstract

Transcription can cause genome instability by promoting R-loop formation but also act as a mutation-suppressing machinery by sensing of DNA lesions leading to the activation of DNA damage signaling and transcription-coupled repair. Recovery of RNA synthesis following the resolution of repair of transcription-blocking lesions is critical to avoid apoptosis and several new factors involved in this process have recently been identified. Some DNA repair proteins are recruited to initiating RNA polymerases and this may expediate the recruitment of other factors that participate in the repair of transcription-blocking DNA lesions. Recent studies have shown that transcription of protein-coding genes does not always give rise to spliced transcripts, opening the possibility that cells may use the transcription machinery in a splicing-uncoupled manner for other purposes including surveillance of the transcribed genome.

Keywords: DNA damage response; Landscape of transcription; R-loops; Splicing-uncoupled transcription; Transcription-coupled repair.

Mateescu, B., Jones, J. C., Alexander, R. P., Alsop, E., An, J. Y., Asghari, M., Boomgarden, A., Bouchareychas, L., Cayota, A., Chang, H. C., Charest, A., Chiu, D. T., Coffey, R. J., Das, S., De Hoff, P., deMello, A., D'Souza-Schorey, C., Elashoff, D., Eliato, K. R., Franklin, J. L., … Tewari, M. (2022). Phase 2 of extracellular RNA communication consortium charts next-generation approaches for extracellular RNA research. iScience, 25(8), 104653. https://doi.org/10.1016/j.isci.2022.104653

Abstract

The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013-2018), Phase 2 of the program (ERCC2, 2019-2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2's current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Keywords: Biochemistry; Biological sciences; Cell biology; Molecular biology.

Palomar, V. M., Jaksich, S., Fujii, S., Kuciński, J., & Wierzbicki, A. T. (2022). High-resolution map of plastid-encoded RNA polymerase binding patterns demonstrates a major role of transcription in chloroplast gene expression. The Plant journal : for cell and molecular biology, 111(4), 1139–1151. https://doi.org/10.1111/tpj.15882

Abstract

Plastids contain their own genomes, which are transcribed by two types of RNA polymerases. One of those enzymes is a bacterial-type, multi-subunit polymerase encoded by the plastid genome. The plastid-encoded RNA polymerase (PEP) is required for efficient expression of genes encoding proteins involved in photosynthesis. Despite the importance of PEP, its DNA binding locations have not been studied on the genome-wide scale at high resolution. We established a highly specific approach to detect the genome-wide pattern of PEP binding to chloroplast DNA using plastid chromatin immunoprecipitation-sequencing (ptChIP-seq). We found that in mature Arabidopsis thaliana chloroplasts, PEP has a complex DNA binding pattern with preferential association at genes encoding rRNA, tRNA, and a subset of photosynthetic proteins. Sigma factors SIG2 and SIG6 strongly impact PEP binding to a subset of tRNA genes and have more moderate effects on PEP binding throughout the rest of the genome. PEP binding is commonly enriched on gene promoters, around transcription start sites. Finally, the levels of PEP binding to DNA are correlated with levels of RNA accumulation, which demonstrates the impact of PEP on chloroplast gene expression. Presented data are available through a publicly available Plastid Genome Visualization Tool (Plavisto) at https://plavisto.mcdb.lsa.umich.edu/.

Keywords: RNA polymerase; plastid; sigma factor; transcription.

McLean, E. K., Nye, T. M., Lowder, F. C., & Simmons, L. A. (2022). The Impact of RNA-DNA Hybrids on Genome Integrity in Bacteria. Annual review of microbiology, 10.1146/annurev-micro-102521-014450. Advance online publication. https://doi.org/10.1146/annurev-micro-102521-014450

Abstract

During the essential processes of DNA replication and transcription, RNA-DNA hybrid intermediates are formed that pose significant risks to genome integrity when left unresolved. To manage RNA-DNA hybrids, all cells rely on RNase H family enzymes that specifically cleave the RNA portion of the many different types of hybrids that form in vivo. Recent experimental advances have provided new insight into how RNA-DNA hybrids form and the consequences to genome integrity that ensue when persistent hybrids remain unresolved. Here we review the types of RNA-DNA hybrids, including R-loops, RNA primers, and ribonucleotide misincorporations, that form during DNA replication and transcription and discuss how each type of hybrid can contribute to genome instability in bacteria. Further, we discuss how bacterial RNase HI, HII, and HIII and bacterial FEN enzymes contribute to genome maintenance through the resolution of hybrids. Expected final online publication date for the Annual Review of Microbiology, Volume 76 is September 2022.

Liu, Y., Munsayac, A., Hall, I., & Keane, S. C. (2022). Solution Structure of NPSL2, A Regulatory Element in the oncomiR-1 RNA. Journal of molecular biology, 167688. Advance online publication. https://doi.org/10.1016/j.jmb.2022.167688

Abstract

The miR-17 ∼ 92a polycistron, also known as oncomiR-1, is commonly overexpressed in multiple cancers and has several oncogenic properties. OncomiR-1 encodes six constituent microRNAs (miRs), each enzymatically processed with different efficiencies. However, the structural mechanism that regulates this differential processing remains unclear. Chemical probing of oncomiR-1 revealed that the Drosha cleavage sites of pri-miR-92a are sequestered in a four-way junction. NPSL2, an independent stem loop element, is positioned just upstream of pri-miR-92a and sequesters a crucial part of the sequence that constitutes the basal helix of pri-miR-92a. Disruption of the NPSL2 hairpin structure could promote the formation of a pri-miR-92a structure that is primed for processing by Drosha. Thus, NPSL2 is predicted to function as a structural switch, regulating pri-miR-92a processing. Here, we determined the solution structure of NPSL2 using solution NMR spectroscopy. This is the first high-resolution structure of an oncomiR-1 element. NPSL2 adopts a hairpin structure with a large, but highly structured, apical and internal loops. The 10-bp apical loop contains a pH-sensitive A+·C mismatch. Additionally, several adenosines within the apical and internal loops have elevated pKa values. The protonation of these adenosines can stabilize the NPSL2 structure through electrostatic interactions. Our study provides fundamental insights into the secondary and tertiary structure of an important RNA hairpin proposed to regulate miR biogenesis.

Keywords: NMR spectroscopy; RNA structure; Thermal denaturation; microRNA.

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