Small circRNAs with self-cleaving ribozymes are frequently expressed in metazoan transcriptomes

Mapping Intimacies ◽

10.1101/721605 ◽

2019 ◽

Author(s):

Amelia Cervera ◽

Marcos De la Pena

Keyword(s):

Rna World ◽

Hammerhead Ribozyme ◽

Circular Rnas ◽

Classical Type ◽

Type I ◽

Ltr Retrotransposons ◽

Animal Tissues ◽

Catalytic Rnas ◽

Human Genomes

Ribozymes are catalytic RNAs present in modern genomes but considered as remnants of a prebiotic RNA world. The paradigmatic hammerhead ribozyme (HHR) is a small self-cleaving motif widespread from bacterial to human genomes. Here, we report that most of the classical type I HHRs frequently found in the genomes of diverse animals are contained within a novel family of non-autonomous non-LTR retrotransposons. These retroelements are expressed as abundant linear and circular RNAs of ~170-400 nt in different animal tissues. In vitro analyses confirm an efficient self-cleavage of the HHRs harboured in invertebrate retrozymes, whereas those in retrozymes of vertebrates, such as the axolotl, require to act as dimeric motifs to reach higher self-cleavage rates. Ligation assays of retrozyme RNAs with a protein ligase versus HHR self-ligation indicate that, most likely, tRNA ligases and not the ribozymes are involved in the step of RNA circularization. Altogether, these results confirm the existence of a new and conserved pathway in animals and, likely, in eukaryotes in general, for the efficient biosynthesis of RNA circles through small ribozymes, which will allow the development of biotechnological tools in the emerging field of circRNAs.

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Small circRNAs with self-cleaving ribozymes are highly expressed in diverse metazoan transcriptomes

Nucleic Acids Research ◽

10.1093/nar/gkaa187 ◽

2020 ◽

Vol 48 (9) ◽

pp. 5054-5064 ◽

Cited By ~ 2

Author(s):

Amelia Cervera ◽

Marcos de la Peña

Keyword(s):

Rna World ◽

Hammerhead Ribozyme ◽

Circular Rnas ◽

Classical Type ◽

Type I ◽

Ltr Retrotransposons ◽

Animal Tissues ◽

Catalytic Rnas ◽

Human Genomes

Abstract Ribozymes are catalytic RNAs present in modern genomes but regarded as remnants of a prebiotic RNA world. The paradigmatic hammerhead ribozyme (HHR) is a small self-cleaving motif widespread from bacterial to human genomes. Here, we report that most of the classical type I HHRs frequently found in the genomes of animals are contained within a novel family of non-autonomous non-LTR retrotransposons of the retrozyme class. These retroelements are expressed as abundant linear and circular RNAs of ∼170-400 nt in different animal tissues. Bioinformatic and in vitro analyses indicate an efficient self-cleavage of the HHRs harboured in most invertebrate retrozymes, whereas HHRs in retrozymes of vertebrates, such as the axolotl and other amphibians, require to act as dimeric motifs to reach higher self-cleavage rates. Ligation assays of retrozyme RNAs with a protein ligase versus HHR self-ligation indicate that, most likely, tRNA ligases and not the ribozymes are involved in the step of RNA circularization. Altogether, these results confirm the existence of a new and conserved pathway in animals and, likely, eukaryotes in general, for the efficient biosynthesis of RNA circles through small ribozymes, which opens the door for the development of new tools in the emerging field of study of circRNAs.

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Relative occupation of type-I and type-II corticosteroid receptors in rat brain following stress and dexamethasone treatment: functional implications

Journal of Endocrinology ◽

10.1677/joe.0.1150459 ◽

1987 ◽

Vol 115 (3) ◽

pp. 459-467 ◽

Cited By ~ 265

Author(s):

J. M. H. M. Reul ◽

F. R. van den Bosch ◽

E. R. de Kloet

Keyword(s):

Rat Brain ◽

Plasma Concentrations ◽

Striking Difference ◽

Classical Type ◽

Type I ◽

Type Ii ◽

Binding Studies ◽

Receptor Sites ◽

Basal Plasma

ABSTRACT The rat brain contains two receptor systems for corticosterone: the type-I corticosterone-preferring receptor and the classical type-II glucocorticoid receptor. The two receptor populations can be distinguished in binding studies with the 'pure' synthetic glucocorticoid 11β,17β-dihydroxy-6-methyl-17α (1-propynyl)-androsta-1,4,6-trione-3-one (RU 28362). In-vitro autoradiography and quantitative image analysis showed that the type-I receptor was localized almost exclusively in the hippocampus, whereas the type-II receptor extended throughout the brain, with the highest levels in the nucleus paraventricularis, nucleus supraopticus and in the thalamic, amygdaloid, hippocampal and septal regions. Unoccupied type-I and type-II receptor sites, as measured in vitro by cytosol binding of 3H-labelled steroids, displayed a large difference in the rate of appearance after adrenalectomy. The availability of type-I receptors exhibited a marked increase, reaching maximal levels within 4–7 h, and then remained constant until 2 weeks after adrenalectomy. The availability of type-II receptors did not change considerably during the first 24 h after adrenalectomy, but displayed a large increase in capacity during the subsequent 2 weeks. After adrenocortical activation as a consequence of exposure to a novel environment, plasma concentrations of corticosterone increased to reach a peak of 811 nmol/l after 30 min and attained the basal concentration (43 nmol/l) after 240 min. During this time, occupation of type-I receptors increased from 77·8% at 0 min to 97% at 30–60 min and then declined to 84·8% after 240 min. Occupation of the type-II receptors was 28·1% at 0 min, 74·5% after 30 min and 32·8% after 240 min. Injection of dexamethasone (25 μg/100 g body wt) at 08.00 h resulted in suppression of basal plasma concentrations of corticosterone and prevented the circadian-driven rise in circulating corticosterone. Occupation of type-I receptors did not change considerably as a result of injection of dexamethasone, but occupation of type-II receptors was markedly increased till 16.00 h compared with that after injection of vehicle. It was concluded that the type-I and type-II receptors are not only localized differently in the rat brain, but also exhibit a striking difference in occupation after manipulation of the pituitary-adrenocortical system. The data further support the concept of a type-I receptor-mediated tonic activating influence and a type-II receptor-mediated feedback action of corticosterone on brain function. J. Endocr. (1987) 115, 459–467

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The AMINO experiment: RNA stability under solar radiation studied on the EXPOSE-R facility of the International Space Station

International Journal of Astrobiology ◽

10.1017/s147355041400024x ◽

2014 ◽

Vol 14 (1) ◽

pp. 99-103 ◽

Cited By ~ 3

Author(s):

Jacques Vergne ◽

Hervé Cottin ◽

Laura da Silva ◽

André Brack ◽

Didier Chaput ◽

...

Keyword(s):

Solar Radiation ◽

International Space Station ◽

Rna World ◽

Rna Stability ◽

Space Station ◽

Careful Examination ◽

International Space ◽

Catalytic Rnas ◽

World Hypothesis

AbstractCareful examination of the present metabolism and in vitro selection of various catalytic RNAs strongly support the RNA world hypothesis as a crucial step of the origins and early life evolution. Small functional RNAs were exposed from 10 March 2009 to 21 January 2011 to space conditions on board the International Space Station in the EXPOSE-R mission. The aim of this study was to investigate the preservation or modification properties such as integrity of RNAs after space exposition. The exposition to the solar radiation has a strong degradation effect on the size distribution of RNA. Moreover, the comparison between the in-flight samples, exposed to the Sun and not exposed, indicates that the solar radiation degrades RNA bases.

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A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

Nature Communications ◽

10.1038/s41467-021-27790-8 ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Griffin M. Schroeder ◽

Chapin E. Cavender ◽

Maya E. Blau ◽

Jermaine L. Jenkins ◽

David H. Mathews ◽

...

Keyword(s):

Rna World ◽

Binding Pocket ◽

Gene Control ◽

Type I ◽

Bacterial Cells ◽

Messenger Rnas ◽

Non Coding Rnas ◽

Effector Recognition ◽

Mediated Catalysis

AbstractRiboswitches are structured non-coding RNAs often located upstream of essential genes in bacterial messenger RNAs. Such RNAs regulate expression of downstream genes by recognizing a specific cellular effector. Although nearly 50 riboswitch classes are known, only a handful recognize multiple effectors. Here, we report the 2.60-Å resolution co-crystal structure of a class I type I preQ1-sensing riboswitch that reveals two effectors stacked atop one another in a single binding pocket. These effectors bind with positive cooperativity in vitro and both molecules are necessary for gene regulation in bacterial cells. Stacked effector recognition appears to be a hallmark of the largest subgroup of preQ1 riboswitches, including those from pathogens such as Neisseria gonorrhoeae. We postulate that binding to stacked effectors arose in the RNA World to closely position two substrates for RNA-mediated catalysis. These findings expand known effector recognition capabilities of riboswitches and have implications for antimicrobial development.

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Conceptus-derived prostaglandins regulate gene expression in the endometrium prior to pregnancy recognition in ruminants

Reproduction ◽

10.1530/rep-13-0165 ◽

2013 ◽

Vol 146 (4) ◽

pp. 377-387 ◽

Cited By ~ 65

Author(s):

Thomas E Spencer ◽

Niamh Forde ◽

Piotr Dorniak ◽

Thomas R Hansen ◽

Jared J Romero ◽

...

Keyword(s):

Gene Expression ◽

Local Effect ◽

Classical Type ◽

Type I ◽

Regulate Gene Expression ◽

Uterine Lumen ◽

Uterine Flushing ◽

Pregnancy Recognition ◽

Regulate Gene

In cattle, the blastocyst hatches from the zona pellucida on days 8–9 and then forms a conceptus that grows and elongates into an ovoid and then filamentous shape between days 9 and 16. The growing conceptus synthesizes and secretes prostaglandins (PGs) and interferon τ (IFNT). Our hypothesis was that the ovoid conceptus exerts a local effect on the endometrium prior to maternal recognition of pregnancy on day 16 in cattle. In study one, synchronized cyclic heifers received no blastocysts or 20in vitro-produced blastocysts on day 7 and their uteri were collected on day 13. IFNT was not detected by RIA in the uterine flushing samples of pregnant heifers containing multiple ovoid conceptuses; however, total PG levels were higher in the uterine lumen of pregnant heifers than in that of cyclic heifers. Microarray analysis revealed that the expression of 44 genes was increased in the endometria of day 13 pregnant heifers when compared with that in the endometria of cyclic heifers, and many of these genes were classical Type I IFN-stimulated genes (ISGs). In studies two and three, the effects of infusing PGs at the levels produced by the elongating day 14 conceptus into the uterine lumen of cyclic ewes on ISG expression in the endometrium were determined. Results indicated that the infusion of PGs increased the abundance of several ISGs in the endometrium. These studies support the hypothesis that the day 13 conceptus secretes PGs that act locally in a paracrine manner to alter gene expression in the endometrium prior to pregnancy recognition in cattle.

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Circular RNA hsa_circRNA_0007334 is Predicted to Promote MMP7 and COL1A1 Expression by Functioning as a miRNA Sponge in Pancreatic Ductal Adenocarcinoma

Journal of Oncology ◽

10.1155/2019/7630894 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 19

Author(s):

Jinghui Yang ◽

Xianling Cong ◽

Ming Ren ◽

Hongyan Sun ◽

Tao Liu ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Expression Profiles ◽

Differentially Expressed ◽

Ductal Adenocarcinoma ◽

Circular Rnas ◽

Type I ◽

Sequencing Analysis ◽

Small Interfering Rnas ◽

Regulatory Pathways

Pancreatic cancer remains one of the leading causes of cancer-related deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor. Many circular RNAs (circRNAs) have proven to play vital roles in the physiological and pathological processes of tumorigenesis; however, their biogenesis in PDAC remains unclear. In this study, the expression profiles of circRNAs from 10 PDAC tissues and their paired adjacent nontumor tissues were analyzed through RNA sequencing analysis. An enrichment analysis was employed to predict the functions of the differentially expressed circRNAs. Sequence alignment information and mRNA microarray projects were used to predict the RNA regulatory network. The knockdown of circRNAs by small interfering RNAs followed by wound healing and western blot assays was used to confirm their functions in a PDAC cell line. A total of 278 circRNAs were identified as differentially expressed in PDAC tissue. Of these, we found that hsa_circRNA_0007334 was significantly upregulated and may serve as a competing endogenous RNA to regulate matrix metallopeptidase 7 (MMP7) and collagen type I alpha 1 chain (COL1A1) by the competitive adsorption of hsa-miR-144-3p and hsa-miR-577 to enhance the expression and functions of MMP7 and COL1A1 in PDAC. In vitro experiments confirmed these results. The present study is the first to propose two regulatory pathways in PDAC: hsa_circRNA_0007334–hsa-miR-144-3p–MMP7 and hsa_circRNA_0007334–hsa-miR-577–COL1A1.

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Collagen fibrillogenesis in vitro: interaction of types I and V collagen

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142670 ◽

1986 ◽

Vol 44 ◽

pp. 210-211

Author(s):

Arthur J. Wasserman ◽

Kathy C. Kloos ◽

David E. Birk

Keyword(s):

Type I Collagen ◽

Corneal Stroma ◽

Minor Component ◽

Homogeneous Distribution ◽

Type I ◽

Type V Collagen ◽

Fibril Morphology ◽

Type V ◽

In Vitro Interaction

Type I collagen is the predominant collagen in the cornea with type V collagen being a quantitatively minor component. However, the content of type V collagen (10-20%) in the cornea is high when compared to other tissues containing predominantly type I collagen. The corneal stroma has a homogeneous distribution of these two collagens, however, immunochemical localization of type V collagen requires the disruption of type I collagen structure. This indicates that these collagens may be arranged as heterpolymeric fibrils. This arrangement may be responsible for the control of fibril diameter necessary for corneal transparency. The purpose of this work is to study the in vitro assembly of collagen type V and to determine whether the interactions of these collagens influence fibril morphology.

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Plasminogen Activation in Diabetes Mellitus: Normalization of Blood Sugar Levels Improves Impaired Enzyme Kinetics In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657861 ◽

1985 ◽

Vol 54 (02) ◽

pp. 413-414 ◽

Cited By ~ 10

Author(s):

Margarethe Geiger ◽

Bernd R Binder

Keyword(s):

Plasminogen Activator ◽

Blood Sugar ◽

Metabolic Disorders ◽

Normal Values ◽

Diabetic Patients ◽

Type I ◽

Plasminogen Activation ◽

Lag Period ◽

Sugar Levels

SummaryWe have demonstrated previously that fibrin enhanced plasmin formation by the vascular plasminogen activator was significantly impaired, when components isolated from the plasma of three uncontrolled diabetic patients (type I) were used to study plasminogen activation in vitro. In the present study it can be demonstrated that functional properties of the vascular plasminogen activators as well as of the plasminogens from the same three diabetic patients are significantly improved after normalization of blood sugar levels and improvement of HbAlc values. Most pronounced the Km of diabetic vascular plasminogen activator in the presence of fibrin returned to normal values, and for diabetic plasminogen the prolonged lag period until maximal plasmin formation occurred was shortened to almost control values. From these data we conclude that the observed abnormalities of in vitro fibrinolysis are not primarily associated with the diabetic disease, but might be secondary to metabolic disorders caused by diabetes.

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