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Article ; Online: 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.

Nahalka, Jozef

International journal of molecular sciences

2024 Volume 25, Issue 8

Abstract: The COVID-19 pandemic prompted rapid research on SARS-CoV-2 pathogenicity. Consequently, new data can be used to advance the molecular understanding of SARS-CoV-2 infection. The present bioinformatics study discusses the "spikeopathy" at the molecular ... ...

Abstract	The COVID-19 pandemic prompted rapid research on SARS-CoV-2 pathogenicity. Consequently, new data can be used to advance the molecular understanding of SARS-CoV-2 infection. The present bioinformatics study discusses the "spikeopathy" at the molecular level and focuses on the possible post-transcriptional regulation of the SARS-CoV-2 spike protein S1 subunit in the host cell/tissue. A theoretical protein-RNA recognition code was used to check the compatibility of the SARS-CoV-2 spike protein S1 subunit with mRNAs in the human transcriptome (1-L transcription). The principle for this method is elucidated on the defined RNA binding protein GEMIN5 (gem nuclear organelle-associated protein 5) and RNU2-1 (U2 spliceosomal RNA). Using the method described here, it was shown that 45% of the genes/proteins identified by 1-L transcription of the SARS-CoV-2 spike protein S1 subunit are directly linked to COVID-19, 39% are indirectly linked to COVID-19, and 16% cannot currently be associated with COVID-19. The identified genes/proteins are associated with stroke, diabetes, and cardiac injury.
MeSH term(s)	Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Humans ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; COVID-19/virology ; COVID-19/metabolism ; COVID-19/genetics ; Transcription, Genetic ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Computational Biology/methods ; Transcriptome
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; RNA, Messenger
Language	English
Publishing date	2024-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25084440
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 1-L Transcription in Parkinson's Disease.

Nahalka, Jozef

Frontiers in bioscience (Landmark edition)

2023 Volume 28, Issue 11, Page(s) 292

Abstract: Background: As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson's disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons ... ...

Abstract	Background: As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson's disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons are affected and microglia are activated. Methods: A theoretical protein-RNA recognition code that assumes that the second letter in codons is compatible with specific amino acids involved in protein-RNA recognition was used to search for compatibility of human α-synuclein (α-syn) with mRNAs in the human transcriptome (1-L transcription). Results: The 1-L transcription revealed compatible amino acid sequences with the ATTTA ARE (class I), PAS and polyA in α-syn, supporting a protein-RNA regulatory model. In PD, inflammatory microglia reactions, cognitive decline and motor circuit disturbances are observed. The model theoretically explains why α-syn producing neurons are less protected from inflammation and why microglia are activated. Consistent with knowledge of PD, the identified genes showed how the PI3K-AKT pathway is downregulated, how reactive oxygen species (ROS) production and sensitivity are increased, how mitochondria are destabilized, why autophagy is impaired, and why neuronal depigmentation is observed. Conclusions: 1-L transcription of α-syn leads to genes/proteins relevant to PD. When α-syn is accepted as a small RNA recognition protein involved in the post-transcriptional regulations, some identified genes indicate that its function is an important regulatory factor associated with intracellular and extracellular transport of RNA vesicles. These vesicles are extremely important in cellular communication. In addition, the spectrum of identified genes strongly indicates that α-syn produced by neuronal cells is required for proper regulation of inflammatory and immune responses.
MeSH term(s)	Humans ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism ; Gene Expression Regulation ; Inflammation/genetics ; Inflammation/metabolism ; Dopaminergic Neurons/metabolism ; RNA/metabolism
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; alpha-Synuclein ; RNA (63231-63-0)
Language	English
Publishing date	2023-12-07
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2811292
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Article ; Online: 1-L Transcription in Parkinson's Disease

Jozef Nahalka

Frontiers in Bioscience-Landmark, Vol 28, Iss 11, p

2023 Volume 292

Abstract: Background: As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson’s disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons are ...

Abstract	Background: As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson’s disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons are affected and microglia are activated. Methods: A theoretical protein-RNA recognition code that assumes that the second letter in codons is compatible with specific amino acids involved in protein-RNA recognition was used to search for compatibility of human α-synuclein (α-syn) with mRNAs in the human transcriptome (1-L transcription). Results: The 1-L transcription revealed compatible amino acid sequences with the ATTTA ARE (class I), PAS and polyA in α-syn, supporting a protein-RNA regulatory model. In PD, inflammatory microglia reactions, cognitive decline and motor circuit disturbances are observed. The model theoretically explains why α-syn producing neurons are less protected from inflammation and why microglia are activated. Consistent with knowledge of PD, the identified genes showed how the PI3K-AKT pathway is downregulated, how reactive oxygen species (ROS) production and sensitivity are increased, how mitochondria are destabilized, why autophagy is impaired, and why neuronal depigmentation is observed. Conclusions: 1-L transcription of α-syn leads to genes/proteins relevant to PD. When α-syn is accepted as a small RNA recognition protein involved in the post-transcriptional regulations, some identified genes indicate that its function is an important regulatory factor associated with intracellular and extracellular transport of RNA vesicles. These vesicles are extremely important in cellular communication. In addition, the spectrum of identified genes strongly indicates that α-syn produced by neuronal cells is required for proper regulation of inflammatory and immune responses.
Keywords	α-synuclein ; bioinformatics method ; identified genes ; parkinson's disease ; protein-rna recognition ; Biochemistry ; QD415-436 ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	IMR Press
Document type	Article ; Online
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Article ; Online: Transcription of the Envelope Protein by 1-L Protein-RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis.

Nahalka, Jozef

Current issues in molecular biology

2022 Volume 44, Issue 2, Page(s) 791–816

Abstract: The theoretical protein-RNA recognition code was used in this study to research the compatibility of the SARS-CoV-2 envelope protein (E) with mRNAs in the human transcriptome. According to a review of the literature, the spectrum of identified genes ... ...

Abstract	The theoretical protein-RNA recognition code was used in this study to research the compatibility of the SARS-CoV-2 envelope protein (E) with mRNAs in the human transcriptome. According to a review of the literature, the spectrum of identified genes showed that the virus post-transcriptionally promotes or represses the genes involved in the SARS-CoV-2 life cycle. The identified genes/proteins are also involved in adaptive immunity, in the function of the cilia and wound healing (EMT and MET) in the pulmonary epithelial tissue, in Alzheimer's and Parkinson's disease and in type 2 diabetes. For example, the E-protein promotes BHLHE40, which switches off the IL-10 inflammatory "brake" and inhibits antiviral T
Language	English
Publishing date	2022-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb44020055
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Article ; Online: 1-L Transcription in Alzheimer's Disease.

Nahalka, Jozef

Current issues in molecular biology

2022 Volume 44, Issue 8, Page(s) 3533–3551

Abstract: Alzheimer's disease is a very complex disease and better explanations and models are needed to understand how neurons are affected and microglia are activated. A new model of Alzheimer's disease is presented here, the β-amyloid peptide is considered an ... ...

Abstract	Alzheimer's disease is a very complex disease and better explanations and models are needed to understand how neurons are affected and microglia are activated. A new model of Alzheimer's disease is presented here, the β-amyloid peptide is considered an important RNA recognition/binding peptide. 1-L transcription revealed compatible sequences with AAUAAA (PAS signal) and UUUC (class III ARE rich in U) in the Aβ peptide, supporting the peptide-RNA regulatory model. When a hypothetical model of fibril selection with the prionic character of amyloid assemblies is added to the peptide-RNA regulatory model, the downregulation of the PI3K-Akt pathway and the upregulation of the PLC-IP3 pathway are well explained. The model explains why neurons are less protected from inflammation and why microglia are activated; why mitochondria are destabilized; why the autophagic flux is destabilized; and why the post-transcriptional attenuation of the axonal signal "noise" is interrupted. For example, the model suggests that Aβ peptide may post-transcriptionally control ELAVL2 (ELAV-like RNA binding protein 2) and DCP2 (decapping mRNA protein 2), which are known to regulate RNA processing, transport, and stability.
Language	English
Publishing date	2022-08-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb44080243
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Article ; Online: Transcription of the Envelope Protein by 1-L Protein–RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis

Jozef Nahalka

Current Issues in Molecular Biology, Vol 44, Iss 55, Pp 791-

2022 Volume 816

Abstract: The theoretical protein–RNA recognition code was used in this study to research the compatibility of the SARS-CoV-2 envelope protein (E) with mRNAs in the human transcriptome. According to a review of the literature, the spectrum of identified genes ... ...

Abstract	The theoretical protein–RNA recognition code was used in this study to research the compatibility of the SARS-CoV-2 envelope protein (E) with mRNAs in the human transcriptome. According to a review of the literature, the spectrum of identified genes showed that the virus post-transcriptionally promotes or represses the genes involved in the SARS-CoV-2 life cycle. The identified genes/proteins are also involved in adaptive immunity, in the function of the cilia and wound healing (EMT and MET) in the pulmonary epithelial tissue, in Alzheimer’s and Parkinson’s disease and in type 2 diabetes. For example, the E-protein promotes BHLHE40, which switches off the IL-10 inflammatory “brake” and inhibits antiviral T H αβ cells. In the viral cycle, E supports the COPII-SCAP-SREBP-HSP90α transport complex by the lowering of cholesterol in the ER and by the repression of insulin signaling, which explains the positive effect of HSP90 inhibitors in COVID-19 (geldanamycin), and E also supports importin α/β-mediated transport to the nucleus, which explains the positive effect of ivermectin, a blocker of importins α/β. In summary, transcription of the envelope protein by the 1-L protein–RNA recognition code leads to genes/proteins that are relevant to the SARS-CoV-2 life cycle and pathogenesis.
Keywords	protein–RNA recognition ; bioinformatics method ; COVID-19 ; SARS-CoV-2 ; identified genes ; envelope protein ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Theoretical Analysis of S, M and N Structural Proteins by the Protein-RNA Recognition Code Leads to Genes/proteins that Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis.

Nahalka, Jozef

Frontiers in genetics

2021 Volume 12, Page(s) 763995

Abstract: In this conceptual review, based on the protein-RNA recognition code, some theoretical sequences were detected in the spike (S), membrane (M) and capsid (N) proteins that may post-transcriptionally regulate the host genes/proteins in immune homeostasis, ... ...

Abstract	In this conceptual review, based on the protein-RNA recognition code, some theoretical sequences were detected in the spike (S), membrane (M) and capsid (N) proteins that may post-transcriptionally regulate the host genes/proteins in immune homeostasis, pulmonary epithelial tissue homeostasis, and lipid homeostasis. According to the review of literature, the spectrum of identified genes/proteins shows that the virus promotes IL1α/β-IL1R1 signaling (type 1 immunity) and immunity defense against helminths and venoms (type 2 immunity). In the alteration of homeostasis in the pulmonary epithelial tissue, the virus blocks the function of cilia and the molecular programs that are involved in wound healing (EMT and MET). Additionally, the protein-RNA recognition method described here identifies compatible sequences in the S1A-domain for the post-transcriptional promotion of PIKFYVE, which is one of the critical factors for SARS-CoV-2 entry to the host cell, and for the post-transcriptional repression of xylulokinase XYLB. A decrease in XYLB product (Xu5P) in plasma was proposed as one of the potential metabolomics biomarkers of COVID-19. In summary, the protein-RNA recognition code leads to protein genes relevant to the SARS-CoV-2 life cycle and pathogenesis.
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.763995
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Article ; Online: The role of the protein-RNA recognition code in neurodegeneration.

Nahalka, Jozef

Cellular and molecular life sciences : CMLS

2019 Volume 76, Issue 11, Page(s) 2043–2058

Abstract: MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post- ... ...

Abstract	MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Research on the association between neurodegeneration and RNA-repeat toxicity provides data that support a protein-RNA recognition code. For example, this code explains why hnRNP H and SFPQ proteins, which are involved in amyotrophic lateral sclerosis, are sequestered by the (GGGGCC)n repeat sequence. Similarly, it explains why MNBL proteins and (CTG)n repeats in RNA, which are involved in myotonic dystrophy, are sequestered into RNA foci. Using this code, proteins involved in diseases can be identified. A simple protein BLAST search of the human genome for amino acid repeats that correspond to the nucleotide repeats reveals new proteins among already known proteins that are involved in diseases. For example, the (CAG)n repeat sequence, when transcribed into possible peptide sequences, leads to the identification of PTCD3, Rem2, MESP2, SYPL2, WDR33, COL23A1, and others. After confirming this approach on RNA repeats, in the next step, the code was used in the opposite manner. Proteins that are involved in diseases were compared with microRNAs involved in those diseases. For example, a reasonable correspondence of microRNA 9 and 107 with amyloid-β-peptide (Aβ42) was identified. In the last step, a miRBase search for micro-nucleotides, obtained by transcription of a prion amino acid sequence, revealed new microRNAs and microRNAs that have previously been identified as involved in prion diseases. This concept provides a useful key for designing RNA or peptide probes.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Binding Sites ; Genetic Code ; Genome, Human ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism ; Humans ; Huntington Disease/genetics ; Huntington Disease/metabolism ; Huntington Disease/pathology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Microsatellite Repeats ; Myotonic Dystrophy/genetics ; Myotonic Dystrophy/metabolism ; Myotonic Dystrophy/pathology ; PTB-Associated Splicing Factor/genetics ; PTB-Associated Splicing Factor/metabolism ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Prion Diseases/genetics ; Prion Diseases/metabolism ; Prion Diseases/pathology ; Protein Binding ; Protein Processing, Post-Translational ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	HNRNPH2 protein, human ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H ; MicroRNAs ; PTB-Associated Splicing Factor ; RNA, Messenger
Language	English
Publishing date	2019-04-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03096-3
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Article ; Online: Insoluble Protein Applications: The Use of Bacterial Inclusion Bodies as Biocatalysts.

Köszagová, Romana / Hrabárová, Eva / Achbergerová, Lucia / Nahálka, Jozef

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2406, Page(s) 501–515

Abstract: Biocatalysis and biotransformations have a broad application in industrial synthetic chemistry. In addition to the whole cell catalysis, purified recombinant enzymes are successfully used for biocatalysis of specific chemical reactions. In this ... ...

Abstract	Biocatalysis and biotransformations have a broad application in industrial synthetic chemistry. In addition to the whole cell catalysis, purified recombinant enzymes are successfully used for biocatalysis of specific chemical reactions. In this contribution, we report characterization, immobilization, and application of several model target enzymes (D-amino acid oxidase, sialic acid aldolase, maltodextrin phosphorylase, polyphosphate kinase, UDP-glucose pyrophosphorylase) physiologically aggregated within inclusion bodies retaining their biological activity as immobilized biocatalysts.
MeSH term(s)	Bacteria/chemistry ; Bacteria/metabolism ; Biocatalysis ; Biotransformation ; Enzymes, Immobilized/chemistry ; Inclusion Bodies
Chemical Substances	Enzymes, Immobilized
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1859-2_30
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Article: Physiologically Aggregated LacZ Applied in Trehalose Galactosylation in a Recycled Batch Mode.

Belkova, Martina / Janegova, Tatiana / Hrabarova, Eva / Nahalka, Jozef

Life (Basel, Switzerland)

2023 Volume 13, Issue 8

Abstract: Galactooligosaccharides obtained via β-galactosidase transgalactosylation have health-promoting properties and are widely recognized as effective prebiotics. Trehalose-based galactooligosaccharides could be introduced into food and pharmaceutical ... ...

Abstract	Galactooligosaccharides obtained via β-galactosidase transgalactosylation have health-promoting properties and are widely recognized as effective prebiotics. Trehalose-based galactooligosaccharides could be introduced into food and pharmaceutical industries similarly to trehalose. In light of this, new technological approaches are needed. Recently, in vivo enzyme immobilizations for recombinant proteins have been introduced, and physiological aggregation into active inclusion bodies (aIBs) has emerged as one such method of in vivo immobilization. To prepare LacZ β-galactosidase in the form of aIBs, we used a short 10 amino acid aggregation-prone tag. These native protein particles were simply washed from the cell lysate and applied in trehalose galactosylation in a recycled batch mode. In this study, aIBs entrapped in alginate beads, encapsulated in alginate/cellulose sulfate/poly(methylene-co-guanidine) capsules and magnetized were compared with free aIBs. Alginate/cellulose sulfate/PMCG capsules showed more suitable properties and applicability for biotransformation of trehalose at its high concentration (25%,
Language	English
Publishing date	2023-07-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13081619
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