Noncoding RNAs: biology and applications—a Keystone Symposia report

Cable, Jennifer; Heard, Edith; Hirose, Tetsuro; Prasanth, Kannanganattu V.; Henninger, Jonathan E.; Quinodoz, Sofia A.; Spector, David L.; Diermeier, Sarah D.; Porman, Allison M.; Kumar, Dhiraj; Feinberg, Mark W.; Shen, Xiaohua; Unfried, Juan P.; Johnson, Rory; Chen, Chun-Kan; Wilusz, Jeremy E.; Lempradl, Adelheid; McGeary, Sean E.; Wahba, Lamia; Pyle, Anna Marie; Hargrove, Amanda E.; Simon, Matthew D.; Marcia, Marco; Przanowska, Roza; Chang, Howard Y.; Jaffrey, Samie R.; Contreras, Lydia M.; Chen, Qi; Shi, Junchao; Mendell, Joshua T.; He, Lin; Song, Erwei; Rinn, John L.; Lalwani, Mukesh Kumar; Kalem, Murat C.; Chuong, Edward B.; Maquat, Lynne; Liu, Xuhang

doi:10.1111/nyas.14713

Cited by 19 publications

(13 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This procedure consisted of i) energy minimization with steepest descent; ii) a 10 ns-long equilibration in the NPT ensemble using the Berendsen barostat 79 at 1 atm; iii) a 10 ns-long equilibration in the NVT ensemble using the Bussi-Donadio-Parrinello thermostat 80 at 300K. During the last two steps, harmonic restraints with harmonic constant equal to 400 kJ/mol/nm 2 were applied to the positions of the RNA backbone as well as probe atoms.…”

Section: Methodsmentioning

confidence: 99%

“…The following settings were implemented using PLUMED. First, the position of the atoms of the RNA backbone in the mother system were communicated to all the replicas with a stride equal to 0.2 ps and the corresponding atoms were restrained to have a maximum RMSD of 0.2 nm from the mother configuration using an upper harmonic wall with intensity equal to 10000 kJ/mol/nm 2 . Second, to accelerate the probe exploration of the RNA surface, we used metadynamics 48 .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN

Panei

Gkeka

Bonomi

2023

Preprint

View full text Add to dashboard Cite

The rational targeting of RNA with small molecules is hampered by our still limited understanding of RNA structural and dynamic properties. Mostin silicotools for binding site identification rely on static structures and therefore cannot face the challenges posed by the dynamic nature of RNA molecules. Here we present SHAMAN, a computational technique to identify potential small-molecule binding sites in RNA structural ensembles. SHAMAN enables exploring the conformational landscape of RNA with atomistic molecular dynamics and at the same time identifying RNA pockets in an efficient way with the aid of probes and enhanced-sampling techniques. In our benchmark composed of large, structured riboswitches as well as small, flexible viral RNAs, SHAMAN successfully identified all the experimentally resolved pockets and ranked them among the most favorite probe hotspots. Overall, SHAMAN sets a solid foundation for future drug design efforts targeting RNA with small molecules, effectively addressing the long-standing challenges in the field.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN

Panei

Gkeka

Bonomi

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…ncRNAs including microRNAs (miRs), small interference RNAs (siRNAs), or long non-coding RNAs (lncRNAs) are involved in the maintenance of cellular homeostasis and the innate immune response to tissue injury or infection. Panel B: While many questions regarding the overall impact of the noncoding genome upon human health and disease are still unanswered [61,62,296], available experimental and clinical evidence so far suggests a limited number of miRs (miR-17-92 cluster, miR-21, miR-142, miRNA-146a, miR-155, miR-181, miR-223) [297] and lncRNAs [1, 2, 298] may constitute therapeutic targets in cardiovascular diseases. For each individual target, however, this depends on ensuring efficient drug targeting and clinical safety [106].…”

Section: New Figure 3 -Key Features Of the Human Noncoding Genome And...mentioning

confidence: 99%

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Poller¹,

Heidecker²,

Ammirati³

et al. 2022

Preprint

View full text Add to dashboard Cite

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

show abstract

“…Noncoding RNAs (ncRNAs) represent a class of RNA molecules that do not encode proteins, including from long noncoding RNAs (lncRNAs) with more than 200 nucleotides to piwi-interacting RNAs (piRNAs) with only 20 nucleotides in terms of length [ 99 ]. This type of RNA can regulate the expression of protein-coding genes; therefore, it is essential to control cell function and identity, and is related to many pathological diseases, particularly cancer [ 100 ].…”

Section: Introductionmentioning

confidence: 99%

Pancreatic cancer stemness: dynamic status in malignant progression

Zhao

Qin

Zhao

et al. 2023

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Pancreatic cancer (PC) is one of the most aggressive malignancies worldwide. Increasing evidence suggests that the capacity for self-renewal, proliferation, and differentiation of pancreatic cancer stem cells (PCSCs) contribute to major challenges with current PC therapies, causing metastasis and therapeutic resistance, leading to recurrence and death in patients. The concept that PCSCs are characterized by their high plasticity and self-renewal capacities is central to this review. We focused specifically on the regulation of PCSCs, such as stemness-related signaling pathways, stimuli in tumor cells and the tumor microenvironment (TME), as well as the development of innovative stemness-targeted therapies. Understanding the biological behavior of PCSCs with plasticity and the molecular mechanisms regulating PC stemness will help to identify new treatment strategies to treat this horrible disease.

show abstract

Noncoding RNAs: biology and applications—a Keystone Symposia report

Cited by 19 publications

References 186 publications

Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN

Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Pancreatic cancer stemness: dynamic status in malignant progression

Contact Info

Product

Resources

About