scholarly journals Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts

2017 ◽  
Author(s):  
Xiaoyu Li ◽  
Xushen Xiong ◽  
Meiling Zhang ◽  
Kun Wang ◽  
Ying Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reverse Transcription ◽  
Translation Efficiency ◽  
Rna Modifications ◽  
Precise Location ◽  
Human Transcriptome ◽  
Functional Studies ◽  
Resolution Mapping ◽  
And Function ◽  
First Time

SUMMARYGene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location, regulation and function. Here, we develop a base-resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in 5’-UTR, particularly those at the first nucleotide of mRNA, associate with increased translation efficiency. A different subset of m1A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome and are dependent on the methyltransferase TRMT6/61A. Additionally, we show for the first time that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation.

Denervation in murine fast-twitch muscle: short-term physiological changes and temporal expression profiling

2006 ◽  
Vol 25 (1) ◽  
pp. 60-74 ◽  
Author(s):  
Anna Raffaello ◽  
Paolo Laveder ◽  
Chiara Romualdi ◽  
Camilla Bean ◽  
Luana Toniolo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Calcium Sensitivity ◽  
Isometric Tension ◽  
Force Frequency ◽  
Functional Studies ◽  
Real Time Quantitative Pcr ◽  
And Function ◽  
Denervated Muscles ◽  
Fast Muscles

Denervation deeply affects muscle structure and function, the alterations being different in slow and fast muscles. Because the effects of denervation on fast muscles are still controversial, and high-throughput studies on gene expression in denervated muscles are lacking, we studied gene expression during atrophy progression following denervation in mouse tibialis anterior (TA). The sciatic nerve was cut close to trochanter in adult CD1 mice. One, three, seven, and fourteen days after denervation, animals were killed and TA muscles were dissected out and utilized for physiological experiments and gene expression studies. Target cDNAs from TA muscles were hybridized on a dedicated cDNA microarray of muscle genes. Seventy-one genes were found differentially expressed. Microarray results were validated, and the expression of relevant genes not probed on our array was monitored by real-time quantitative PCR (RQ-PCR). Nuclear- and mitochondrial-encoded genes implicated in energy metabolism were consistently downregulated. Among genes implicated in muscle contraction (myofibrillar and sarcoplasmic reticulum), genes typical of fast fibers were downregulated, whereas those typical of slow fibers were upregulated. Electrophoresis and Western blot showed less pronounced changes in myofibrillar protein expression, partially confirming changes in gene expression. Isometric tension of skinned fibers was little affected by denervation, whereas calcium sensitivity decreased. Functional studies in mouse extensor digitorum longus muscle showed prolongation in twitch time parameters and shift to the left in force-frequency curves after denervation. We conclude that, if studied at the mRNA level, fast muscles appear not less responsive than slow muscles to the interruption of neural stimulation.

scholarly journals The origin, fate and function of macrophages in the peripheral nervous system—an update

2020 ◽  
Vol 32 (11) ◽  
pp. 709-717 ◽  
Author(s):  
Lukas Amann ◽  
Marco Prinz
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Rna Sequencing ◽  
Peripheral Nervous System ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
New Techniques ◽  
Macrophage Populations ◽  
And Function ◽  
First Time

Abstract The field of macrophage biology has made enormous progress over recent years. This was triggered by the advent of several new techniques such as the establishment of Cre/loxP-based transgenic mouse models that allowed for the first time delineation of the ontogeny and function of specific macrophage populations across many tissues. In addition, the introduction of new high-throughput technologies like bulk RNA sequencing and later single-cell RNA sequencing as well as advances in epigenetic analysis have helped to establish gene expression profiles, enhancer landscapes and local signaling cues that define and shape the identity of diverse macrophage populations. Nonetheless, some macrophage populations, like the ones residing in the peripheral nervous system (PNS), have not been studied in such detail yet. Here, we discuss recent studies that shed new light on the ontogeny, heterogeneity and gene expression profiles of resident macrophages in peripheral nerves and described differential activation of macrophage subsets during and after acute sciatic nerve injury.

scholarly journals Evaluation of the Role of ITGBL1 in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2676
Author(s):  
Alexander Jorge Cortez ◽  
Katarzyna Aleksandra Kujawa ◽  
Agata Małgorzata Wilk ◽  
Damian Robert Sojka ◽  
Joanna Patrycja Syrkis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Culture Media ◽  
Global Gene Expression ◽  
Cellular Adhesion ◽  
Mrna Isoforms ◽  
Functional Studies ◽  
Matrix Organization ◽  
Global Gene Expression Analysis ◽  
And Function

In our previous microarray study we identified two subgroups of high-grade serous ovarian cancers with distinct gene expression and survival. Among differentially expressed genes was an Integrin beta-like 1 (ITGBL1), coding for a poorly characterized protein comprised of ten EGF-like repeats. Here, we have analyzed the influence of ITGBL1 on the phenotype of ovarian cancer (OC) cells. We analyzed expression of four putative ITGBL1 mRNA isoforms in five OC cell lines. OAW42 and SKOV3, having the lowest level of any ITGBL1 mRNA, were chosen to produce ITGBL1-overexpressing variants. In these cells, abundant ITGBL1 mRNA expression could be detected by RT-PCR. Immunodetection was successful only in the culture media, suggesting that ITGBL1 is efficiently secreted. We found that ITGBL1 overexpression affected cellular adhesion, migration and invasiveness, while it had no effect on proliferation rate and the cell cycle. ITGBL1-overexpressing cells were significantly more resistant to cisplatin and paclitaxel, major drugs used in OC treatment. Global gene expression analysis revealed that signaling pathways affected by ITGBL1 overexpression were mostly those related to extracellular matrix organization and function, integrin signaling, focal adhesion, cellular communication and motility; these results were consistent with the findings of our functional studies. Overall, our results indicate that higher expression of ITGBL1 in OC is associated with features that may worsen clinical course of the disease.

scholarly journals 5-Methylcytosine RNA Modifications Promote Retrovirus Replication in an ALYREF Reader Protein-Dependent Manner

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Matthew Eckwahl ◽  
Ruyi Xu ◽  
Julia Michalkiewicz ◽  
Wen Zhang ◽  
Pooja Patel ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Rna Stability ◽  
Translation Efficiency ◽  
Dependent Manner ◽  
Rna Modifications ◽  
Nucleotide Resolution ◽  
And Function ◽  
Murine Leukemia ◽  
Retrovirus Replication

ABSTRACT RNA modifications play diverse roles in regulating RNA function, and viruses co-opt these pathways for their own benefit. While recent studies have highlighted the importance of N6-methyladenosine (m6A)—the most abundant mRNA modification—in regulating retrovirus replication, the identification and function of other RNA modifications in viral biology have been largely unexplored. Here, we characterized the RNA modifications present in a model retrovirus, murine leukemia virus (MLV), using mass spectrometry and sequencing. We found that 5-methylcytosine (m5C) is highly enriched in viral genomic RNA relative to uninfected cellular mRNAs, and we mapped at single-nucleotide resolution the m5C sites, which are located in multiple clusters throughout the MLV genome. Further, we showed that the m5C reader protein ALYREF plays an important role in regulating MLV replication. Together, our results provide a complete m5C profile in a virus and its function in a eukaryotic mRNA. IMPORTANCE Over 130 modifications have been identified in cellular RNAs, which play critical roles in many cellular processes, from modulating RNA stability to altering translation efficiency. One such modification, 5-methylcytosine, is relatively abundant in mammalian mRNAs, but its precise location and function are not well understood. In this study, we identified unexpectedly high levels of m5C in the murine leukemia virus RNA, precisely mapped its location, and showed that ALYREF, a reader protein that specifically recognizes m5C, regulates viral production. Together, our findings provide a high-resolution atlas of m5C in murine leukemia virus and reveal a functional role of m5C in viral replication.

scholarly journals Expression of psbA1 gene in Synechocystis sp. PCC 6803 is influenced by CO2

2017 ◽  
Vol 12 (1) ◽  
pp. 156-161
Author(s):  
Ciprian Chiş ◽  
Dalton Carmel ◽  
luliana Chiş ◽  
Aurel Ardelean ◽  
Nicolae Dragos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Photosystem Ii ◽  
Inorganic Carbon ◽  
Microaerobic Conditions ◽  
Almost All ◽  
And Function ◽  
First Time ◽  
Encoding Genes ◽  
Synechocystis Sp ◽  
Pcc 6803

AbstractIn almost all cyanobacteria a small gene family encodes the photosystem II reaction center D1 proteins that play vital roles in the cell. Recently, several types of this protein were functionally characterised and the conditions for their transcript regulation were identified. One of the D1-encoding genes previously believed to be silent is induced by microaerobic conditions. This gene was first described in Synechocystis sp. PCC 6803 as psbA1 encoding the D1 isoform. When Synechocystis cells are shifted from high to ambient level CO2 we recorded an increase in gene expression, similar, but to a lesser extent, to microaerobic conditions. When synthetic air is used to remove the ambient CO2, the induction of the gene is absent. We documented for the first time that expression of a psbA gene is regulated by the inorganic carbon status of the cell. Our conclusion is that both CO2 and microaerobic conditions are independently influencing the expression of psbA1 gene in Synechocystis sp. PCC 6803. Hence, it is crucial to understand the mechanisms of regulation and function of D1 proteins as it could be used for future bio-technological applications as a virtual tool-box for modulating the function of PSII.

scholarly journals The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Paz Nombela ◽  
Borja Miguel-López ◽  
Sandra Blanco
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Therapeutic Potential ◽  
Biological Processes ◽  
Rna Modifications ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
Made In

AbstractRNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

scholarly journals Better expression profile of CD8 and CD4 gene in uterus of pregnant ewe in comparison to non-pregnant - a novel report

2020 ◽  
Author(s):  
Md Mofijul Islam ◽  
Aruna Pal ◽  
Partha Das ◽  
Samiddha Banerjee
Keyword(s):  
Gene Expression ◽  
Expression Profile ◽  
Expression Profiling ◽  
Cd4 T Cell ◽  
Cell Compartment ◽  
Maternal Environment ◽  
Differential Gene ◽  
Pregnant Ewe ◽  
And Function ◽  
First Time

AbstractCD8 and CD4 T cells play a central role in the immune response to viruses and intracellular pathogens as well as functions for the maintenance of both the mother and fetus. The present study was conducted to explore the differential gene expression profile for CD8 and CD4 present in the uterus with reference to the gravid and non-gravid Garole sheep and confirmation through immuno histochemical studies. Better CD8 and CD4 gene expression was observed in the mid uterus of pregnant ewes compared to that of non-pregnant ewes, where CD8 expression was better to that of CD4. Gene expression profiling of CD8 and CD4 are reported here for the first time in sheep. CD8 and CD4 expression may be regarded as the useful factor for maintenance of pregnancy. The current observations demonstrate that during pregnancy in ewe the immune system may respond to changes in the maternal environment to maintain the size and function of the CD8 and CD4 T-cell compartment. CD8 and CD4 expression may be employed as marker for pregnancy detection in sheep, which remains always a challenge for sheep breeders.

scholarly journals OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Joel Hrit ◽  
Leeanne Goodrich ◽  
Cheng Li ◽  
Bang-An Wang ◽  
Ji Nie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Embryonic Stem ◽  
Nutrient Sensing ◽  
Zebrafish Embryos ◽  
Hematopoetic Stem Cell ◽  
Tet Enzymes ◽  
And Function ◽  
Necessary And Sufficient ◽  
First Time

TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET2 and 5-methylcytosine, which is accompanied by alterations in gene expression. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.

scholarly journals OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development

2018 ◽  
Author(s):  
Joel Hrit ◽  
Cheng Li ◽  
Elizabeth Allene Martin ◽  
Eric Simental ◽  
Mary Goll ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Weight ◽  
Embryonic Stem ◽  
Nutrient Sensing ◽  
Zebrafish Embryos ◽  
Hematopoetic Stem Cell ◽  
Tet Enzymes ◽  
And Function ◽  
First Time

AbstractTET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a domain of TET1 responsible for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that the TET1-OGT interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET-containing high molecular weight complexes and causes widespread gene expression changes. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.

scholarly journals Epitranscriptomic Signatures in lncRNAs and Their Possible Roles in Cancer

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 52 ◽  
Author(s):  
Sorina Dinescu ◽  
Simona Ignat ◽  
Andreea Lazar ◽  
Carolina Constantin ◽  
Monica Neagu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Modifications ◽  
Chemical Modifications ◽  
Chemically Modified ◽  
Additional Layer ◽  
Expression Control ◽  
Gene Expression Control ◽  
Level Of Knowledge ◽  
Non Coding Rnas ◽  
And Function

In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs are post-transcriptional regulators of gene expression, but RNA modifications occurring in lncRNAs generate an additional layer of gene expression control. Chemical modifications that have been reported in correlation with lncRNAs include m6A, m5C and pseudouridylation. Up to date, several chemically modified long non-coding transcripts have been identified and associated with different pathologies, including cancers. This review presents the current level of knowledge on the most studied cancer-related lncRNAs, such as the metastasis associated lung adenocarcinoma transcript 1 (MALAT1), the Hox transcript antisense intergenic RNA (HOTAIR), or the X-inactive specific transcript (XIST), as well as more recently discovered forms, and their potential roles in different types of cancer. Understanding how these RNA modifications occur, and the correlation between lncRNA changes in structure and function, may open up new therapeutic possibilities in cancer.

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