The chemical identity of RNA molecules beyond the four standard ribonucleosides has fascinated scientists since pseudouridine was characterized as the “fifth” ribonucleotide in 1951. Since then, the ...ever‐increasing number and complexity of modified ribonucleosides have been found in viruses and throughout all three domains of life. Such modifications can be as simple as methylations, hydroxylations, or thiolations, complex as ring closures, glycosylations, acylations, or aminoacylations, or unusual as the incorporation of selenium. While initially found in transfer and ribosomal RNAs, modifications also exist in messenger RNAs and noncoding RNAs. Modifications have profound cellular outcomes at various levels, such as altering RNA structure or being essential for cell survival or organism viability. The aberrant presence or absence of RNA modifications can lead to human disease, ranging from cancer to various metabolic and developmental illnesses such as Hoyeraal–Hreidarsson syndrome, Bowen–Conradi syndrome, or Williams–Beuren syndrome. In this review article, we summarize the characterization of all 143 currently known modified ribonucleosides by describing their taxonomic distributions, the enzymes that generate the modifications, and any implications in cellular processes, RNA structure, and disease. We also highlight areas of active research, such as specific RNAs that contain a particular type of modification as well as methodologies used to identify novel RNA modifications.
This article is categorized under:
RNA Processing > RNA Editing and Modification
Adenosine, guanosine, cytidine, and uridine can be modified at various positions (red) with a myriad of functional groups (outside circle).
Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an abundant nuclear-localized long noncoding RNA (lncRNA) that has significant roles in cancer. While the interacting partners ...and evolutionary sequence conservation of MALAT1 have been examined, much of the structure of MALAT1 is unknown. Here, we propose a hypothetical secondary structural model for 8425 nucleotides of human MALAT1 using three experimental datasets that probed RNA structures in vitro and in various human cell lines. Our model indicates that approximately half of human MALAT1 is structured, forming 194 helices, 13 pseudoknots, five structured tetraloops, nine structured internal loops, and 13 intramolecular long-range interactions that give rise to several multiway junctions. Evolutionary conservation and covariation analyses support 153 of 194 helices in 51 mammalian MALAT1 homologs and 42 of 194 helices in 53 vertebrate MALAT1 homologs, thereby identifying an evolutionarily conserved core that likely has important functional roles in mammals and vertebrates. Data mining revealed that RNA modifications, somatic cancer-associated mutations, and single-nucleotide polymorphisms may induce structural rearrangements that sequester or expose binding sites for several cancer-associated microRNAs. Our findings reveal new mechanistic leads into the roles of MALAT1 by identifying several intriguing structure-function relationships in which the dynamic structure of MALAT1 underlies its biological functions.
Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including ...cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvature-dependent sorting of Piezo1 directly reveals the in situ nano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of calcium, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.
Social media platforms offer unique opportunities for patients and families to provide real-time feedback on their healthcare experiences. Consumer-generated social media ratings of hospitals tend to ...reflect the more subjective aspects of inpatient care experiences; however, evidence on nursing home care is extremely limited.
We collected consumer-reported 5-star ratings of Maryland nursing homes posted from July 2015 to July 2017 on 4 popular social media or online review sites (Facebook, Yelp, Google Consumer Reviews, and Caring.com). We determined if the average score of social media ratings was associated with experience-of-care ratings derived from survey of family members or other responsible parties of nursing home residents, and with "Nursing Home Compare" (NHC) 5-star ratings and individual quality measures.
One hundred ninety-six out of 206 nursing homes in Maryland were reviewed on at least one site and thus had one or more star ratings posted. The overall ratings were 3.11 on average on these sites and 3.03 on the NHC website, with a Pearson correlation of 0.41 (p < 0.001) between the 2 sets of ratings. The correlations between the social media rating and survey-based experience-of-care ratings ranged from 0.40 to 0.60, and the correlations between the social media rating and individual NHC quality measures of citations, nurse staffing, and complaints were about 0.35 (in absolute values). The social media rating also predicted well NHC and experience-of-care measures after adjusting for nursing home covariates and market competition.
The 5-star ratings collected from 4 social networking sites was correlated with and predictive of the NHC and survey-based experience-of-care measures for Maryland nursing homes.
The impact of microbiome in animal physiology is well appreciated, but characterization of animal-microbe symbiosis in marine environments remains a growing need. This study characterizes the ...microbial communities associated with the moon jellyfish Aurelia coerulea, first isolated from the East Pacific Ocean and has since been utilized as an experimental system. We find that the microbiome of this Pacific Aurelia culture is dominated by two taxa, a Mollicutes and Rickettsiales. The microbiome is stable across life stages, although composition varies. Mining the host sequencing data, we assembled the bacterial metagenome-assembled genomes (MAGs). The bacterial MAGs are highly reduced, and predict a high metabolic dependence on the host. Analysis using multiple metrics suggest that both bacteria are likely new species. We therefore propose the names Ca. Mariplasma lunae (Mollicutes) and Ca. Marinirickettsia aquamalans (Rickettsiales). Finally, comparison with studies of Aurelia from other geographical populations suggests the association with Ca. Mariplasma lunae occurs in Aurelia from multiple geographical locations. The low-diversity microbiome of Aurelia provides a relatively simple system to study host-microbe interactions.
Abstract
Recent studies suggest noncoding RNAs interact with genomic DNA, forming an RNA•DNA–DNA triple helix that regulates gene expression. However, base triplet composition of pyrimidine motif ...RNA•DNA–DNA triple helices is not well understood beyond the canonical U•A–T and C•G–C base triplets. Using native gel-shift assays, the relative stability of 16 different base triplets at a single position, Z•X–Y (where Z = C, U, A, G and X–Y = A–T, G–C, T–A, C–G), in an RNA•DNA–DNA triple helix was determined. The canonical U•A–T and C•G–C base triplets were the most stable, while three non-canonical base triplets completely disrupted triple-helix formation. We further show that our RNA•DNA–DNA triple helix can tolerate up to two consecutive non-canonical A•G–C base triplets. Additionally, the RNA third strand must be at least 19 nucleotides to form an RNA•DNA–DNA triple helix but increasing the length to 27 nucleotides does not increase stability. The relative stability of 16 different base triplets in DNA•DNA–DNA and RNA•RNA–RNA triple helices was distinctly different from those in RNA•DNA–DNA triple helices, showing that base triplet stability depends on strand composition being DNA and/or RNA. Multiple factors influence the stability of triple helices, emphasizing the importance of experimentally validating formation of computationally predicted triple helices.
Our goal is to explore quantitative motor features in critically ill patients with severe brain injury (SBI). We hypothesized that computational decoding of these features would yield information on ...underlying neurological states and outcomes. Using wearable microsensors placed on all extremities, we recorded a median 24.1 (IQR: 22.8-25.1) hours of high-frequency accelerometry data per patient from a prospective cohort (n = 69) admitted to the ICU with SBI. Models were trained using time-, frequency-, and wavelet-domain features and levels of responsiveness and outcome as labels. The two primary tasks were detection of levels of responsiveness, assessed by motor sub-score of the Glasgow Coma Scale (GCSm), and prediction of functional outcome at discharge, measured with the Glasgow Outcome Scale-Extended (GOSE). Detection models achieved significant (AUC: 0.70 95% CI: 0.53-0.85) and consistent (observation windows: 12 min-9 h) discrimination of SBI patients capable of purposeful movement (GCSm > 4). Prediction models accurately discriminated patients of upper moderate disability or better (GOSE > 5) with 2-6 h of observation (AUC: 0.82 95% CI: 0.75-0.90). Results suggest that time series analysis of motor activity yields clinically relevant insights on underlying functional states and short-term outcomes in patients with SBI.
Advancements in novel combination immunotherapies as well as innovative downstream management courses offer great optimism for the applicability of emerging cancer immunotherapy to prospective ...treatment of cold tumours. This review comprehensively analyses and discusses notable current research directions in the field and underscores future directions for continued scientific progress alongside relevant clinical applications. Vitiligo is an autoimmune disorder characterised by white depigmented cutaneous macules. Although vitiligo may generally be considered a cosmetic disease, literature has associated broader systemic comorbidities, including a higher risk for atherosclerotic events, dyslipidaemia, and cardiovascular risk. To the authors’ knowledge, this is the first systematic review that assesses the association between vitiligo and cardiovascular disease (CVD)/CVD-associated factors. Utilising the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors searched PubMed and Scopus databases to identify studies available as of 30th June 2022, examining CVD and CVD-associated risk factors in patients with vitiligo. Of 2,553 articles, seven studies (four cross-sectional and three case-control), totalling 611 patients diagnosed with vitiligo (56.3% female), met the inclusion criteria for the authors’ review. Six studies suggested a significant association between patients with vitiligo and an increased risk for CVD via increased atherosclerotic events, constraint-induced movement therapy, plaque presence, dyslipidaemia, high-sensitivity C-reactive protein, oxidative stress, as well as decreased levels of vitamin D, calcium, zinc, and antioxidants. However, one study found that patients with vitiligo presented with fewer cardiovascular risk factors and increased levels of high-density lipoprotein. Although few studies indicated an increase in atherosclerotic risk due to elevated low-density lipoprotein-cholesterol and total cholesterol, contradictory high-density lipoprotein and total cholesterol levels in additional studies indicate the need for further investigation. Lastly, the association between vitiligo severity and CVD risk also indicated conflicting results. The authors’ small sample size restrained their ability to compare populations and incorporate racial and ethnic diversity to generalise their conclusions. Additional studies are required to comprehensively understand the association between vitiligo and the risk of CVD.
Background
Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma ...with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs.
Methods
PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta‐Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random‐effects model.
Results
Eight observational studies (3 cohort and 5 case–control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0–71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51–0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38–0.94) and GBC was 0.78 (95% CI: 0.68–0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66–1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69–0.88) and 0.70 (95% CI: 0.61–0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non‐steroidal anti‐inflammatory drugs (aRR: 0.80, 95% CI: 0.72–0.89) and metformin (aRR: 0.80, 95% CI: 0.72–0.90).
Conclusions
Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.
Statins associate with lower risk of biliary tract cancers: a systematic review and meta‐analysis.
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