scholarly journals Dynamic temperature-sensitive A-to-I RNA editing in the brain of a heterothermic mammal during hibernation

2018 ◽  
Author(s):  
Kent A. Riemondy ◽  
Austin E. Gillen ◽  
Emily A. White ◽  
Lori K. Bogren ◽  
Jay R. Hesselberth ◽  
...  
Keyword(s):  
Amino Acids ◽  
Body Temperature ◽  
Rna Editing ◽  
Cold Exposure ◽  
Environmental Changes ◽  
Critical Role ◽  
Brain Regions ◽  
Ground Squirrels ◽  
Temperature Sensitive ◽  
Repeat Elements

ABSTRACTRNA editing diversifies genomically encoded information to expand the complexity of the transcriptome. In ectothermic organisms, including Drosophila and Cephalopoda, where body temperature mirrors ambient temperature, decreases in environmental temperature lead to increases in A-to-I RNA editing and cause amino acid recoding events that are thought to be adaptive responses to temperature fluctuations. In contrast, endothermic mammals, including humans and mice, typically maintain a constant body temperature despite environmental changes. Here, A-to-I editing primarily targets repeat elements, rarely results in the recoding of amino acids and plays a critical role in innate immune tolerance. Hibernating ground squirrels provide a unique opportunity to examine RNA editing in a heterothermic mammal whose body temperature varies over 30°C and can be maintained at 5°C for many days during torpor. We profiled the transcriptome in three brain regions at six physiological states to quantify RNA editing and determine whether cold-induced RNA editing modifies the transcriptome as a potential mechanism for neuroprotection at low temperature during hibernation. We identified 5,165 A-to-I editing sites in 1,205 genes with dynamically increased editing after prolonged cold exposure. The majority (99.6%) of the cold-increased editing sites are outside of previously annotated coding regions, 82.7% lie in SINE-derived repeats, and 12 sites are predicted to recode amino acids. Additionally, A-to-I editing frequencies increase with increasing cold-exposure demonstrating that ADAR remains active during torpor. Our findings suggest that dynamic A-to-I editing at low body temperature may provide a neuroprotective mechanism to limit aberrant dsRNA accumulation during torpor in the mammalian hibernator.

scholarly journals Site to site detection and analysis of C-to-U RNA editing in rice mitochondria-encoded ORFs

2020 ◽  
Author(s):  
Peng Zheng ◽  
Yuqing Huang ◽  
Hao Chen ◽  
Hao Du ◽  
Jumin Tu
Keyword(s):  
Signal Transduction ◽  
Amino Acids ◽  
Rna Editing ◽  
Environmental Changes ◽  
Organelle Biogenesis ◽  
Functional Consequence ◽  
Precise Information ◽  
Evolutionarily Conserved ◽  
Conserved Amino Acids ◽  
Biological Context

Abstract Background Cytidine to uridine (C-to-U) RNA editing is an important type of substitutional RNA editing. In plants, C-to-U modification is almost omnipresent in chloroplasts and mitochondria, where it mainly serves to restore evolutionarily conserved amino acids by changing the codon information. The important roles that C-to-U RNA editing plays in organelle biogenesis, adaptation to environmental changes, and signal transduction have been confirmed in different plant species. In rice mitochondria, 491 C-to-U editing sites have been identified previously, and case studies have elucidated the function of several C-to-U editing sites in rice, but the functional consequence of most C-to-U alteration need to be investigated further. Results Here, we totally identified 539 C-to-U editing sites in rice mitochondria-encoded ORFs, 87.2% of these editing sites were observed on the first or the second base of a codon, resulting in the alteration of encoded amino acid. Moreover, we found some novel editing sites and several inaccurately annotated sites which may be functionally important, with the support of the highly conserved amino acids encoded by these edited codons. Finally, we annotated all 539 C-to-U RNA editing sites in their biological context. Conclusions We detected 539 C-to-U editing sites in rice mitochondria-encoded ORFs and annotated them with more precise information, which will facilitate our investigation on the function of C-to-U editing events in rice.

ADAPTATION OF WHITE MICE (MUS MUSCULUS) TO REPEATED COOLING

1967 ◽  
Vol 45 (3) ◽  
pp. 321-327 ◽  
Author(s):  
David M. Ogilvie
Keyword(s):  
Body Temperature ◽  
Rectal Temperature ◽  
Cold Exposure ◽  
Mus Musculus ◽  
Room Temperature ◽  
The Body ◽  
Progressive Decrease

The effects, on the body temperature of white mice, of repeated short exposures to cold were investigated using two methods of restraint. Animals held in a flattened posture became hypothermic at room temperature, cooled more than five times as fast at −10 °C as mice that could adopt a heat-conserving posture, and continued to cool for some time after they were removed from the cold. With repeated tests, cooling at room temperature decreased, and an improvement in re warming ability was observed. In addition, with lightly restrained mice, the fall in rectal temperature during cold exposure showed a progressive decrease, a phenomenon not observed with severely restrained animals.

scholarly journals ADeditome provides the genomic landscape of A-to-I RNA editing in Alzheimer’s disease

2021 ◽  
Author(s):  
Sijia Wu ◽  
Mengyuan Yang ◽  
Pora Kim ◽  
Xiaobo Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rna Editing ◽  
Memory Loss ◽  
Brain Regions ◽  
Disease Stage ◽  
Mirna Regulation ◽  
Annotation Database ◽  
Functional Annotations ◽  
Genomic Landscape

Abstract A-to-I RNA editing, contributing to nearly 90% of all editing events in human, has been reported to involve in the pathogenesis of Alzheimer’s disease (AD) due to its roles in brain development and immune regulation, such as the deficient editing of GluA2 Q/R related to cell death and memory loss. Currently, there are urgent needs for the systematic annotations of A-to-I RNA editing events in AD. Here, we built ADeditome, the annotation database of A-to-I RNA editing in AD available at https://ccsm.uth.edu/ADeditome, aiming to provide a resource and reference for functional annotation of A-to-I RNA editing in AD to identify therapeutically targetable genes in an individual. We detected 1676 363 editing sites in 1524 samples across nine brain regions from ROSMAP, MayoRNAseq and MSBB. For these editing events, we performed multiple functional annotations including identification of specific and disease stage associated editing events and the influence of editing events on gene expression, protein recoding, alternative splicing and miRNA regulation for all the genes, especially for AD-related genes in order to explore the pathology of AD. Combing all the analysis results, we found 108 010 and 26 168 editing events which may promote or inhibit AD progression, respectively. We also found 5582 brain region-specific editing events with potentially dual roles in AD across different brain regions. ADeditome will be a unique resource for AD and drug research communities to identify therapeutically targetable editing events. Significance: ADeditome is the first comprehensive resource of the functional genomics of individual A-to-I RNA editing events in AD, which will be useful for many researchers in the fields of AD pathology, precision medicine, and therapeutic researches.

scholarly journals SEN1, a positive effector of tRNA-splicing endonuclease in Saccharomyces cerevisiae.

1992 ◽  
Vol 12 (5) ◽  
pp. 2154-2164 ◽  
Author(s):  
D J DeMarini ◽  
M Winey ◽  
D Ursic ◽  
F Webb ◽  
M R Culbertson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Amino Acid ◽  
Gene Product ◽  
Signal Sequence ◽  
Null Alleles ◽  
Nucleoside Triphosphate ◽  
Temperature Sensitive ◽  
Yeast Saccharomyces Cerevisiae ◽  
Amino Terminal

The SEN1 gene, which is essential for growth in the yeast Saccharomyces cerevisiae, is required for endonucleolytic cleavage of introns from all 10 families of precursor tRNAs. A mutation in SEN1 conferring temperature-sensitive lethality also causes in vivo accumulation of pre-tRNAs and a deficiency of in vitro endonuclease activity. Biochemical evidence suggests that the gene product may be one of several components of a nuclear-localized splicing complex. We have cloned the SEN1 gene and characterized the SEN1 mRNA, the SEN1 gene product, the temperature-sensitive sen1-1 mutation, and three SEN1 null alleles. The SEN1 gene corresponds to a 6,336-bp open reading frame coding for a 2,112-amino-acid protein (molecular mass, 239 kDa). Using antisera directed against the C-terminal end of SEN1, we detect a protein corresponding to the predicted molecular weight of SEN1. The SEN1 protein contains a leucine zipper motif, consensus elements for nucleoside triphosphate binding, and a potential nuclear localization signal sequence. The carboxy-terminal 1,214 amino acids of the SEN1 protein are essential for growth, whereas the amino-terminal 898 amino acids are dispensable. A sequence of approximately 500 amino acids located in the essential region of SEN1 has significant similarity to the yeast UPF1 gene product, which is involved in mRNA turnover, and the mouse Mov-10 gene product, whose function is unknown. The mutation that creates the temperature-sensitive sen1-1 allele is located within this 500-amino-acid region, and it causes a substitution for an amino acid that is conserved in all three proteins.

Body temperature regulation and oxygen consumption in young chicks fed thyroid hormone

1991 ◽  
Vol 69 (7) ◽  
pp. 1842-1847 ◽  
Author(s):  
Gregory K. Snyder ◽  
Joseph R. Coelho ◽  
Dalan R. Jensen
Keyword(s):  
Oxygen Consumption ◽  
Thyroid Hormone ◽  
Body Temperature ◽  
Ambient Temperature ◽  
Cold Exposure ◽  
Elevated Serum ◽  
Body Temperatures ◽  
Serum Thyroid Hormone ◽  
Regulate Body Temperature ◽  
Young Chicks

In chicks the ability to regulate body temperature to adult levels develops during the first 2 weeks of life. We examined whether the ability of young chicks to regulate body temperature is increased by elevated levels of the thyroid hormone 3,3′5-triiodothyronine. By 13 days following hatch, body temperatures of chicks were not significantly different from those expected for adult birds. Furthermore, at an ambient temperature of 10 °C, 13-day-old control chicks were able to maintain body temperature, and elevated serum thyroid hormone levels did not increase rates of oxygen consumption or body temperature above control values. Six-day-old chicks had body temperatures that were significantly lower than those of the 13-day-old chicks and were not able to regulate body temperature when exposed to an ambient temperature of 10 °C. On the other hand, 6-day-old chicks with elevated serum thyroid hormone had significantly higher rates of oxygen consumption than 6-day-old control chicks, and were able to maintain constant body temperatures during cold exposure. The increased oxygen consumption rates and improved ability to regulate body temperature during cold exposure were correlated with increased citrate synthase activity in skeletal muscle. Our results support the argument that thyroid hormones play an important role in the development of thermoregulatory ability in neonate birds by stimulating enzyme activities associated with aerobic metabolism.

scholarly journals Tracking the Cartoon mouse phenotype: Hemopexin domain–dependent regulation of MT1-MMP pericellular collagenolytic activity

2018 ◽  
Vol 293 (21) ◽  
pp. 8113-8127 ◽  
Author(s):  
Moustafa Sakr ◽  
Xiao-Yan Li ◽  
Farideh Sabeh ◽  
Tamar Y. Feinberg ◽  
John J. G. Tesmer ◽  
...  
Keyword(s):  
Cell Surface ◽  
Critical Role ◽  
Collagenolytic Activity ◽  
Temperature Sensitive ◽  
Type I ◽  
Permissive Temperature ◽  
Sensitive Mutant ◽  
Temperature Sensitive Mutant ◽  
Golgi Network ◽  
Hemopexin Domain

Following ENU mutagenesis, a phenodeviant line was generated, termed the “Cartoon mouse,” that exhibits profound defects in growth and development. Cartoon mice harbor a single S466P point mutation in the MT1-MMP hemopexin domain, a 200-amino acid segment that is thought to play a critical role in regulating MT1-MMP collagenolytic activity. Herein, we demonstrate that the MT1-MMPS466P mutation replicates the phenotypic status of Mt1-mmp–null animals as well as the functional characteristics of MT1-MMP−/− cells. However, rather than a loss-of-function mutation acquired as a consequence of defects in MT1-MMP proteolytic activity, the S466P substitution generates a misfolded, temperature-sensitive mutant that is abnormally retained in the endoplasmic reticulum (ER). By contrast, the WT hemopexin domain does not play a required role in regulating MT1-MMP trafficking, as a hemopexin domain-deletion mutant is successfully mobilized to the cell surface and displays nearly normal collagenolytic activity. Alternatively, when MT1-MMPS466P–expressing cells are cultured at a permissive temperature of 25 °C that depresses misfolding, the mutant successfully traffics from the ER to the trans-Golgi network (ER → trans-Golgi network), where it undergoes processing to its mature form, mobilizes to the cell surface, and expresses type I collagenolytic activity. Together, these analyses define the Cartoon mouse as an unexpected gain-of-abnormal function mutation, wherein the temperature-sensitive mutant phenocopies MT1-MMP−/− mice as a consequence of eliciting a specific ER → trans-Golgi network trafficking defect.

The Validity of Temperature-Sensitive Ingestible Capsules for Measuring Core Body Temperature in Laboratory Protocols

2011 ◽  
Vol 28 (8) ◽  
pp. 719-726 ◽  
Author(s):  
David Darwent ◽  
Xuan Zhou ◽  
Cameron van den Heuvel ◽  
Charli Sargent ◽  
Greg D. Roach
Keyword(s):  
Body Temperature ◽  
Core Body Temperature ◽  
Temperature Sensitive ◽  
Core Body

What's hot and what's not: defining torpor in free-ranging birds and mammals

2001 ◽  
Vol 79 (10) ◽  
pp. 1885-1890 ◽  
Author(s):  
Robert MR Barclay ◽  
Cori L Lausen ◽  
Lydia Hollis
Keyword(s):  
Body Temperature ◽  
The Body ◽  
Temperature Sensitive ◽  
The Past ◽  
Data Loggers ◽  
Temperature Thresholds ◽  
Radio Transmitters ◽  
Species Specific ◽  
Free Ranging ◽  
Lowered Body

With the development of small implantable data loggers and externally attached temperature-sensitive radio transmitters, increasing attention is being paid to determining the thermoregulatory strategies of free-ranging birds and mammals. One of the constraints of such studies is that without a direct measure of metabolic rate, it is difficult to determine the significance of lowered body temperatures. We surveyed the literature and found that many different definitions have been used to discriminate torpor from normothermy. Many studies use arbitrary temperature thresholds without regard for the normothermic body temperature of the individuals or species involved. This variation makes comparison among studies difficult and means that ecologically and energetically significant small reductions in body temperature may be overlooked. We suggest that normothermic body temperature for each individual animal should be determined and that torpor be defined as occurring when the body temperature drops below that level. When individuals' active temperatures are not available, a species-specific value should be used. Of greater value, however, are the depth and duration of torpor bouts. We suggest several advantages of this definition over those used in the past.

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