scholarly journals Eukaryotic 5-methylcytosine (m5C) RNA Methyltransferases: Mechanisms, Cellular Functions, and Links to Disease

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 102 ◽  
Author(s):  
Katherine Bohnsack ◽  
Claudia Höbartner ◽  
Markus Bohnsack
Keyword(s):  
Dna Methyltransferase ◽  
Nuclear Gene ◽  
Rna Modification ◽  
Messenger Rnas ◽  
Cellular Functions ◽  
Transfer Rnas ◽  
Nuclear Gene Expression ◽  
Genes Encoding ◽  
Biochemical Analyses ◽  
Sun Domain

5-methylcytosine (m5C) is an abundant RNA modification that’s presence is reported in a wide variety of RNA species, including cytoplasmic and mitochondrial ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), as well as messenger RNAs (mRNAs), enhancer RNAs (eRNAs) and a number of non-coding RNAs. In eukaryotes, C5 methylation of RNA cytosines is catalyzed by enzymes of the NOL1/NOP2/SUN domain (NSUN) family, as well as the DNA methyltransferase homologue DNMT2. In recent years, substrate RNAs and modification target nucleotides for each of these methyltransferases have been identified, and structural and biochemical analyses have provided the first insights into how each of these enzymes achieves target specificity. Functional characterizations of these proteins and the modifications they install have revealed important roles in diverse aspects of both mitochondrial and nuclear gene expression. Importantly, this knowledge has enabled a better understanding of the molecular basis of a number of diseases caused by mutations in the genes encoding m5C methyltransferases or changes in the expression level of these enzymes.

scholarly journals The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1758 ◽  
Author(s):  
Anitha Chellamuthu ◽  
Steven G. Gray
Keyword(s):  
Mammalian Cells ◽  
Dna Methyltransferase ◽  
Critical Role ◽  
Messenger Rnas ◽  
Small Cell Lung ◽  
Regulate Gene Expression ◽  
Transfer Rnas ◽  
Epigenetic Modifier ◽  
Recent Developments ◽  
Sun Domain

5-methylcytosine is often associated as an epigenetic modifier in DNA. However, it is also found increasingly in a plethora of RNA species, predominantly transfer RNAs, but increasingly found in cytoplasmic and mitochondrial ribosomal RNAs, enhancer RNAs, and a number of long noncoding RNAs. Moreover, this modification can also be found in messenger RNAs and has led to an increasing appreciation that RNA methylation can functionally regulate gene expression and cellular activities. In mammalian cells, the addition of m5C to RNA cytosines is carried out by enzymes of the NOL1/NOP2/SUN domain (NSUN) family as well as the DNA methyltransferase homologue DNMT2. In this regard, NSUN2 is a critical RNA methyltransferase for adding m5C to mRNA. In this review, using non-small cell lung cancer and other cancers as primary examples, we discuss the recent developments in the known functions of this RNA methyltransferase and its potential critical role in cancer.

scholarly journals Overexpression of chloroplast-targeted ferrochelatase 1 results in a genomes uncoupled chloroplast-to-nucleus retrograde signalling phenotype

2020 ◽  
Vol 375 (1801) ◽  
pp. 20190401 ◽  
Author(s):  
Mike T. Page ◽  
Tania Garcia-Becerra ◽  
Alison G. Smith ◽  
Matthew J. Terry
Keyword(s):  
Gene Expression ◽  
Feedback Inhibition ◽  
Nuclear Gene ◽  
Signalling Pathway ◽  
Chloroplast Genes ◽  
Nuclear Gene Expression ◽  
Retrograde Signalling ◽  
Genes Encoding ◽  
Retrograde Signal

Chloroplast development requires communication between the progenitor plastids and the nucleus, where most of the genes encoding chloroplast proteins reside. Retrograde signals from the chloroplast to the nucleus control the expression of many of these genes, but the signalling pathway is poorly understood. Tetrapyrroles have been strongly implicated as mediators of this signal with the current hypothesis being that haem produced by the activity of ferrochelatase 1 (FC1) is required to promote nuclear gene expression. We have tested this hypothesis by overexpressing FC1 and specifically targeting it to either chloroplasts or mitochondria, two possible locations for this enzyme. Our results show that targeting of FC1 to chloroplasts results in increased expression of the nuclear-encoded chloroplast genes GUN4 , CA1 , HEMA1 , LHCB2.1, CHLH after treatment with Norflurazon (NF) and that this increase correlates to FC1 gene expression and haem production measured by feedback inhibition of protochlorophyllide synthesis. Targeting FC1 to mitochondria did not enhance the expression of nuclear-encoded chloroplast genes after NF treatment. The overexpression of FC1 also increased nuclear gene expression in the absence of NF treatment, demonstrating that this pathway is operational in the absence of a stress treatment. Our results therefore support the hypothesis that haem synthesis is a promotive chloroplast-to-nucleus retrograde signal. However, not all FC1 overexpression lines enhanced nuclear gene expression, suggesting there is still a lot we do not understand about the role of FC1 in this signalling pathway. This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.

scholarly journals Coordination of plastid and nuclear gene expression

2003 ◽  
Vol 358 (1429) ◽  
pp. 135-145 ◽  
Author(s):  
John C. Gray ◽  
James A. Sullivan ◽  
Jun-Hui Wang ◽  
Cheryl A. Jerome ◽  
Daniel MacLean
Keyword(s):  
Nuclear Gene ◽  
Nuclear Genes ◽  
Regulation Of Transcription ◽  
Nuclear Gene Expression ◽  
Plastid Genomes ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Coordinated Expression ◽  
Plastid Protein ◽  
Related Proteins

The coordinated expression of genes distributed between the nuclear and plastid genomes is essential for the assembly of functional chloroplasts. Although the nucleus has a pre–eminent role in controlling chloroplast biogenesis, there is considerable evidence that the expression of nuclear genes encoding photosynthesis–related proteins is regulated by signals from plastids. Perturbation of several plastid–located processes, by inhibitors or in mutants, leads to decreased transcription of a set of nuclear photosynthesis–related genes. Characterization of arabidopsis gun ( genomes uncoupled ) mutants, which express nuclear genes in the presence of norflurazon or lincomycin, has provided evidence for two separate signalling pathways, one involving tetrapyrrole biosynthesis intermediates and the other requiring plastid protein synthesis. In addition, perturbation of photosynthetic electron transfer produces at least two different redox signals, as part of the acclimation to altered light conditions. The recognition of multiple plastid signals requires a reconsideration of the mechanisms of regulation of transcription of nuclear genes encoding photosynthesis–related proteins.

Chloroplast-mediated regulation of nuclear genes in Arabidopsis thaliana in the absence of light stress

2006 ◽  
Vol 25 (1) ◽  
pp. 142-152 ◽  
Author(s):  
Mirva Piippo ◽  
Yagut Allahverdiyeva ◽  
Virpi Paakkarinen ◽  
Ulla-Maija Suoranta ◽  
Natalia Battchikova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Photosystem I ◽  
Redox State ◽  
Light Stress ◽  
Calvin Cycle ◽  
Nuclear Gene ◽  
Fixation Rate ◽  
Plastoquinone Pool ◽  
Nuclear Gene Expression ◽  
Genes Encoding

Chloroplast signaling involves mechanisms to relay information from chloroplasts to the nucleus, to change nuclear gene expression in response to environmental cues. Aside from reactive oxygen species (ROS) produced under stress conditions, changes in the reduction/oxidation state of photosynthetic electron transfer components or coupled compounds in the stroma and the accumulation of photosynthesis-derived metabolites are likely origins of chloroplast signals. We attempted to investigate the origin of the signals from chloroplasts in mature Arabidopsis leaves by differentially modulating the redox states of the plastoquinone pool and components on the reducing side of photosystem I, as well as the rate of CO2 fixation, while avoiding the production of ROS by excess light. Differential expression of several nuclear photosynthesis genes, including a set of Calvin cycle enzymes, was recorded. These responded to the stromal redox conditions under prevailing light conditions but were independent of the redox state of the plastoquinone pool. The steady-state CO2 fixation rate was reflected in the orchestration of the expression of a number of genes encoding cytoplasmic proteins, including several glycolysis genes and the trehalose-6-phosphate synthase gene, and also the chloroplast-targeted chaperone DnaJ. Clearly, in mature leaves, the redox state of the compounds on the reducing side of photosystem I is of greater importance in light-dependent modulation of nuclear gene expression than the redox state of the plastoquinone pool, particularly at early signaling phases. It also became apparent that photosynthesis-mediated generation of metabolites or signaling molecules is involved in the relay of information from chloroplast to nucleus.

Localisation of inositol trisphosphate and ryanodine receptors during mouse spermatogenesis: possible functional implications

Zygote ◽  
1998 ◽  
Vol 6 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Claudia L. Treviño ◽  
Celia M. Santi ◽  
Carmen Beltrán ◽  
Arturo Hernández-Cruz ◽  
Alberto Darszon ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ryanodine Receptors ◽  
Distribution Patterns ◽  
Mature Sperm ◽  
Messenger Rnas ◽  
Spermatogenic Cells ◽  
Cellular Functions ◽  
Functional Responses ◽  
Genes Encoding ◽  
Intracellular Ca

During spermatogenesis the activity of intracellular Ca2+-release channels is likely to play an important role in different specific cellular functions. Accordingly, messenger RNAs for the three inositol 1,4,5-trisphosphate receptor (IP3R) subtypes were found to be present throughout spermatogenesis. Immunocytochemical analysis revealed distinct distribution patterns of the mature IP3Rs during sperm differentiation. At early stages, IP3Rs are distributed throughout the cytoplasm, and as differentiation proceeds they become selectively localised to the Golgi complex. Consistently, spermatogonia underwent large intracellular Ca2+ release in response to thapsigargin (TG), while smaller responses were detected in late spermatocytes and spermatids. The distribution of IP3Rs and the larger Ca2+-release responses found in spermatogonia, suggest that IP3Rs may be involved in cell proliferation at this stage. This notion is supported by our observations in a spermatogenic cell line that depletion of intracellular Ca2+ pools using TG inhibits cell division, and that incubation with an IP3R-I antisense oligonucleotide completely inhibited proliferation. Furthermore, the three genes encoding ryanodine receptor proteins (RyRs) are expressed at all stages of spermatogenesis. However, immunocytochemical studies with specific antibodies against each of the RyR subtypes detected types 1 and 3 in spermatogenic cells and only type 3 in mature sperm. In contrast to IP3Rs, RyRs remain scattered in the cytoplasm throughout differentiation. Functional responses to caffeine and ryanodine were absent in spermatogenic cells and in mature sperm. These findings suggest that IP3Rs have significantly more important roles in spermatogenesis than RyRs, and that one of these roles is crucial for cell proliferation.

PINK1 and Parkin: team players in stress-induced mitophagy

2020 ◽  
Vol 401 (6-7) ◽  
pp. 891-899 ◽  
Author(s):  
Verian Bader ◽  
Konstanze F. Winklhofer
Keyword(s):  
Wide Spectrum ◽  
Nuclear Gene ◽  
Cellular Functions ◽  
Iron Sulfur Cluster ◽  
Major Mechanism ◽  
Nuclear Gene Expression ◽  
Iron Sulfur ◽  
Innate Immune Signaling ◽  
Molecular Patterns ◽  
Synthesis Regulation

AbstractMitochondria are highly vulnerable organelles based on their complex biogenesis, entailing dependence on nuclear gene expression and efficient import strategies. They are implicated in a wide spectrum of vital cellular functions, including oxidative phosphorylation, iron-sulfur cluster synthesis, regulation of calcium homeostasis, and apoptosis. Moreover, damaged mitochondria can release mitochondrial components, such as mtDNA or cardiolipin, which are sensed as danger-associated molecular patterns and trigger innate immune signaling. Thus, dysfunctional mitochondria pose a thread not only to the cellular but also to the organismal integrity. The elimination of dysfunctional and damaged mitochondria by selective autophagy, called mitophagy, is a major mechanism of mitochondrial quality control. Certain types of stress-induced mitophagy are regulated by the mitochondrial kinase PINK1 and the E3 ubiquitin ligase Parkin, which are both linked to autosomal recessive Parkinson’s disease.

scholarly journals Inosine in Biology and Disease

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 600
Author(s):  
Sundaramoorthy Srinivasan ◽  
Adrian Gabriel Torres ◽  
Lluís Ribas de Pouplana
Keyword(s):  
Human Health ◽  
Purine Biosynthesis ◽  
Messenger Rnas ◽  
Transfer Rnas ◽  
Functional Roles ◽  
Codon Recognition ◽  
Wobble Position ◽  
Biosynthesis Gene ◽  
The Stability ◽  
Cell Signaling Pathways

The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post-transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of tRNA anticodons, inosine profoundly modifies codon recognition, while in mRNA, inosines can modify the sequence of the translated polypeptide or modulate the stability, localization, and splicing of transcripts. Inosine is also found in non-coding and exogenous RNAs, where it plays key structural and functional roles. In addition, molecular inosine is an important secondary metabolite in purine metabolism that also acts as a molecular messenger in cell signaling pathways. Here, we review the functional roles of inosine in biology and their connections to human health.

The oxen Gene of Drosophila Encodes a Homolog of Subunit 9 of Yeast Ubiquinol-Cytochrome c Oxidoreductase Complex: Evidence for Modulation of Gene Expression in Response to Mitochondrial Activity

Genetics ◽  
2000 ◽  
Vol 156 (4) ◽  
pp. 1727-1736 ◽  
Author(s):  
Maxim V Frolov ◽  
Elizaveta V Benevolenskaya ◽  
James A Birchler
Keyword(s):  
Gene Expression ◽  
Cytochrome C ◽  
Cellular Response ◽  
Insertion Site ◽  
Nuclear Gene ◽  
Mutant Phenotype ◽  
P Element ◽  
Mitochondrial Activity ◽  
Genes Encoding ◽  
Subunit 9

Abstract A P-element insertion in the oxen gene, ox1, has been isolated in a search for modifiers of white gene expression. The mutation preferentially exerts a negative dosage effect upon the expression of three genes encoding ABC transporters involved in pigment precursor transport, white, brown, and scarlet. A precise excision of the P element reverts the mutant phenotype. Five different transcription units were identified around the insertion site. To distinguish a transcript responsible for the mutant phenotype, a set of deletions within the oxen region was generated. Analysis of gene expression within the oxen region in the case of deletions as well as generation of transgenic flies allowed us to identify the transcript responsible for oxen function. It encodes a 6.6-kD homolog of mitochondrial ubiquinol cytochrome c oxidoreductase (QCR9), subunit 9 of the bc1 complex in yeast. In addition to white, brown, and scarlet, oxen regulates the expression of three of seven tested genes. Thus, our data provide additional evidence for a cellular response to changes in mitochondrial function. The oxen mutation provides a model for the genetic analysis in multicellular organisms of the effect of mitochondrial activity on nuclear gene expression.

scholarly journals Thioredoxin-dependent control balances the metabolic activities of tetrapyrrole biosynthesis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniel Wittmann ◽  
Neha Sinha ◽  
Bernhard Grimm
Keyword(s):  
Environmental Changes ◽  
Nuclear Gene ◽  
Tetrapyrrole Biosynthesis ◽  
Nuclear Gene Expression ◽  
Light Levels ◽  
Organ Specific ◽  
Intracellular Compartments ◽  
The Face ◽  
Metabolic Activities ◽  
The Impact

AbstractPlastids are specialized organelles found in plants, which are endowed with their own genomes, and differ in many respects from the intracellular compartments of organisms belonging to other kingdoms of life. They differentiate into diverse, plant organ-specific variants, and are perhaps the most versatile organelles known. Chloroplasts are the green plastids in the leaves and stems of plants, whose primary function is photosynthesis. In response to environmental changes, chloroplasts use several mechanisms to coordinate their photosynthetic activities with nuclear gene expression and other metabolic pathways. Here, we focus on a redox-based regulatory network composed of thioredoxins (TRX) and TRX-like proteins. Among multiple redox-controlled metabolic activities in chloroplasts, tetrapyrrole biosynthesis is particularly rich in TRX-dependent enzymes. This review summarizes the effects of plastid-localized reductants on several enzymes of this pathway, which have been shown to undergo dithiol-disulfide transitions. We describe the impact of TRX-dependent control on the activity, stability and interactions of these enzymes, and assess its contribution to the provision of adequate supplies of metabolic intermediates in the face of diurnal and more rapid and transient changes in light levels and other environmental factors.

Chloroplast Redox Control of Nuclear Gene Expression—A New Class of Plastid Signals in Interorganellar Communication

2003 ◽  
Vol 5 (1) ◽  
pp. 95-101 ◽  
Author(s):  
Thomas Pfannschmidt ◽  
Katia Schütze ◽  
Vidal Fey ◽  
Irena Sherameti ◽  
Ralf Oelmüller
Keyword(s):  
Gene Expression ◽  
Nuclear Gene ◽  
Redox Control ◽  
New Class ◽  
Nuclear Gene Expression
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