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Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition
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Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 15849

Special Issue Editor

Dr. Andrey Turchinovich

E-Mail Website1 Website2
Guest Editor
1. Department of Cardiovascular Research, Heidelberg University, 69117 Heidelberg, Germany
2. Heidelberg Biolabs GmbH, 69120 Heidelberg, Germany
Interests: regulation of gene expression; non-coding RNA; cell-free RNA; cancer biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Regulation of mRNA transcription is a highly dynamic process mediated by various molecular events which include specific DNA–protein, RNA–protein, RNA-RNA as well as DNA–RNA interactions. This complex process can be controlled at several steps, including the initial recruitment and assembly of the transcriptional machinery, transcription initiation, transcription pausing, transcription elongation, as well as termination phases. In addition, regulation of mRNA biogenesis and degradation involves the participation of various non-coding RNAs (ncRNAs), such as microRNAs, endogenous siRNAs, small nuclear RNAs, long ncRNAs, circular RNAs, and enhancer RNAs. This Special Issue focuses on the roles of different classes of RNAs and proteins regulating mRNA expression in various cell types. In particular, studies involving advanced deep sequencing, proteomics, and novel bioinformatics algorithms for RNA research are highly welcomed. The formats for submission include original research reports, reviews, and communications.

Dr. Andrey Turchinovich
Guest Editor

Manuscript Submission Information

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Keywords

  • transcriptoion factors (TFs)
  • cis-regulatory elements (CREs)
  • long non-coding RNAs (lncRNAs)
  • short non-coding RNAs (sncRNAs)
  • small nuclear RNAs (snRNAs)
  • microRNA (miRNA)
  • circular RNA (circRNA)
  • DNA methylation
  • chromatin regulators

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Related Special Issue

Published Papers (7 papers)

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Research

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17 pages, 2545 KiB  
Article
miR-30c-5p Gain and Loss of Function Modulate Sciatic Nerve Injury-Induced Nucleolar Stress Response in Dorsal Root Ganglia Neurons
by Raquel Francés, Jorge Mata-Garrido, Miguel Lafarga, María A. Hurlé and Mónica Tramullas
Int. J. Mol. Sci. 2024, 25(21), 11427; https://doi.org/10.3390/ijms252111427 - 24 Oct 2024
Viewed by 1017
Abstract
Neuropathic pain is a prevalent and debilitating chronic syndrome that is often resistant to treatment. It frequently arises as a consequence of damage to first-order nociceptive neurons in the lumbar dorsal root ganglia (DRG), with chromatolysis being the primary neuropathological response following sciatic [...] Read more.
Neuropathic pain is a prevalent and debilitating chronic syndrome that is often resistant to treatment. It frequently arises as a consequence of damage to first-order nociceptive neurons in the lumbar dorsal root ganglia (DRG), with chromatolysis being the primary neuropathological response following sciatic nerve injury (SNI). Nevertheless, the function of miRNAs in modulating this chromatolytic response in the context of neuropathic pain remains unexplored. Our previous research demonstrated that the intracisternal administration of a miR-30c mimic accelerates the development of neuropathic pain, whereas the inhibition of miR-30c prevents pain onset and reverses established allodynia. In the present study, we sought to elucidate the role of miR-30c-5p in the pathogenesis of neuropathic pain, with a particular focus on its impact on DRG neurons following SNI. The organisation and ultrastructural changes in DRG neurons, particularly in the protein synthesis machinery, nucleolus, and Cajal bodies (CBs), were analysed. The results demonstrated that the administration of a miR-30c-5p mimic exacerbates chromatolytic damage and nucleolar stress and induces CB depletion in DRG neurons following SNI, whereas the administration of a miR-30c-5p inhibitor alleviates these effects. We proposed that three essential cellular responses—nucleolar stress, CB depletion, and chromatolysis—are the pathological mechanisms in stressed DRG neurons underlying neuropathic pain. Moreover, miR-30c-5p inhibition has a neuroprotective effect by reducing the stress response in DRG neurons, which supports its potential as a therapeutic target for neuropathic pain management. This study emphasises the importance of miR-30c-5p in neuropathic pain pathogenesis and supports further exploration of miRNA-based treatments. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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21 pages, 18311 KiB  
Article
Single-Cell Transcriptome Analysis Reveals Development-Specific Networks at Distinct Synchronized Antral Follicle Sizes in Sheep Oocytes
by Yukun Song, Nan Zhang, Yu Zhang, Junlan Wang, Qi Lv and Jiaxin Zhang
Int. J. Mol. Sci. 2024, 25(2), 910; https://doi.org/10.3390/ijms25020910 - 11 Jan 2024
Viewed by 1622
Abstract
The development of the ovarian antral follicle is a complex, highly regulated process. Oocytes orchestrate and coordinate the development of mammalian ovarian follicles, and the rate of follicular development is governed by a developmental program intrinsic to the oocyte. Characterizing oocyte signatures during [...] Read more.
The development of the ovarian antral follicle is a complex, highly regulated process. Oocytes orchestrate and coordinate the development of mammalian ovarian follicles, and the rate of follicular development is governed by a developmental program intrinsic to the oocyte. Characterizing oocyte signatures during this dynamic process is critical for understanding oocyte maturation and follicular development. Although the transcriptional signature of sheep oocytes matured in vitro and preovulatory oocytes have been previously described, the transcriptional changes of oocytes in antral follicles have not. Here, we used single-cell transcriptomics (SmartSeq2) to characterize sheep oocytes from small, medium, and large antral follicles. We characterized the transcriptomic landscape of sheep oocytes during antral follicle development, identifying unique features in the transcriptional atlas, stage-specific molecular signatures, oocyte-secreted factors, and transcription factor networks. Notably, we identified the specific expression of 222 genes in the LO, 8 and 6 genes that were stage-specific in the MO and SO, respectively. We also elucidated signaling pathways in each antral follicle size that may reflect oocyte quality and in vitro maturation competency. Additionally, we discovered key biological processes that drive the transition from small to large antral follicles, revealing hub genes involved in follicle recruitment and selection. Thus, our work provides a comprehensive characterization of the single-oocyte transcriptome, filling a gap in the mapping of the molecular landscape of sheep oogenesis. We also provide key insights into the transcriptional regulation of the critical sizes of antral follicular development, which is essential for understanding how the oocyte orchestrates follicular development. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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18 pages, 1538 KiB  
Article
RNA Pol II Assembly Affects ncRNA Expression
by Ana I. Garrido-Godino, Ishaan Gupta, Vicent Pelechano and Francisco Navarro
Int. J. Mol. Sci. 2024, 25(1), 507; https://doi.org/10.3390/ijms25010507 - 29 Dec 2023
Viewed by 1284
Abstract
RNA pol II assembly occurs in the cytoplasm before translocation of the enzyme to the nucleus. Affecting this assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In [...] Read more.
RNA pol II assembly occurs in the cytoplasm before translocation of the enzyme to the nucleus. Affecting this assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In this work, we show that impairment of RNA pol II assembly leads to a decrease in cryptic non-coding RNAs (preferentially CUTs and SUTs). This alteration is partially restored upon overcoming the assembly defect. Notably, this drop in ncRNAs is only partially dependent on the nuclear exosome, which suggests a major specific effect of enzyme assembly. Our data also point out a defect in transcription termination, which leads us to propose that CTD phosphatase Rtr1 could be involved in this process. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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16 pages, 2449 KiB  
Article
Transcriptomic Analysis of Metarhizium anisopliae-Induced Immune-Related Long Non-Coding RNAs in Polymorphic Worker Castes of Solenopsis invicta
by Junaid Zafar, Hongxin Wu, Yating Xu, Liangjie Lin, Zehong Kang, Jie Zhang, Ruonan Zhang, Yongyue Lu, Fengliang Jin and Xiaoxia Xu
Int. J. Mol. Sci. 2023, 24(18), 13983; https://doi.org/10.3390/ijms241813983 - 12 Sep 2023
Cited by 1 | Viewed by 1433
Abstract
Long non-coding RNAs (lncRNAs) represent a class of RNA molecules that do not encode proteins. Generally studied for their regulatory potential in model insects, relatively little is known about their immunoregulatory functions in different castes of eusocial insects, including Solenopsis invicta, a [...] Read more.
Long non-coding RNAs (lncRNAs) represent a class of RNA molecules that do not encode proteins. Generally studied for their regulatory potential in model insects, relatively little is known about their immunoregulatory functions in different castes of eusocial insects, including Solenopsis invicta, a notoriously invasive insect pest. In the current study, we used Metarhizium anisopliae, an entomopathogenic fungus, to infect the polymorphic worker castes (Major and Minor Workers) and subjected them to RNA sequencing at different intervals (6, 24, and 48 h post-infection (hpi)). Comprehensive bioinformatic analysis identified 5719 (1869 known and 3850 novel) lncRNAs in all libraries. Genomic characteristics analysis showed that S. invicta lncRNAs exhibited structural similarities with lncRNAs from other eusocial insects, including lower exon numbers, shorter intron and exon lengths, and a lower expression profile. A comparison of lncRNAs in major and minor worker ants revealed that several lncRNAs were exclusively expressed in one worker caste and remained absent in the other. LncRNAs such as MSTRG.12029.1, XR_005575440.1 (6 h), MSTRG.16728.1, XR_005575440.1 (24 h), MSTRG.20263.41, and MSTRG.11994.5 (48 h) were only present in major worker ants, while lncRNAs such as MSTRG.8896.1, XR_005574239.1 (6 h), MSTRG.20289.8, XR_005575051.1 (24 h), MSTRG.20289.8, and MSTRG.6682.1 (48 h) were only detected in minor workers. Additionally, we performed real-time quantitative PCR and experimentally validated these findings. Functional annotation of cis-acting lncRNAs in major worker ants showed that lncRNAs targeted genes such as serine protease, trypsin, melanization protease-1, spaetzle-3, etc. In contrast, apoptosis and autophagy-related genes were identified as targets of lncRNAs in minor ants. Lastly, we identified several lncRNAs as precursors of microRNAs (miRNAs), such as miR-8, miR-14, miR-210, miR-6038, etc., indicating a regulatory relationship between lncRNAs, miRNAs, and mRNAs in antifungal immunity. These findings will serve as a genetic resource for lncRNAs in polymorphic eusocial ants and provide a theoretical basis for exploring the function of lncRNAs from a unique and novel perspective. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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Review

Jump to: Research

14 pages, 710 KiB  
Review
Regulation of HTT mRNA Biogenesis: The Norm and Pathology
by Alexandra E. Zubkova and Dmitry V. Yudkin
Int. J. Mol. Sci. 2024, 25(21), 11493; https://doi.org/10.3390/ijms252111493 - 26 Oct 2024
Viewed by 683
Abstract
Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the HTT gene, leading to the formation of a toxic variant of the huntingtin protein. It is a rare but severe hereditary disease for [...] Read more.
Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the HTT gene, leading to the formation of a toxic variant of the huntingtin protein. It is a rare but severe hereditary disease for which no effective treatment method has been found yet. The primary therapeutic targets include the mutant protein and the mutant mRNA of HTT. Current clinical trial approaches in gene therapy involve the application of splice modulation, siRNA, or antisense oligonucleotides for RNA-targeted knockdown of HTT. However, these approaches do not take into account the diversity of HTT transcript isoforms in the normal conditions and in HD. In this review, we discuss the features of transcriptional regulation and processing that lead to the formation of various HTT mRNA variants, each of which may uniquely contribute to the progression of the disease. Furthermore, understanding the role of known transcription factors of HTT in pathology may aid in the development of potentially new therapeutic tools based on endogenous regulators. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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17 pages, 2808 KiB  
Review
A Comprehensive Study of MicroRNA in Baculoviruses
by Lucas Federico Motta, Carolina Susana Cerrudo and Mariano Nicolás Belaich
Int. J. Mol. Sci. 2024, 25(1), 603; https://doi.org/10.3390/ijms25010603 - 3 Jan 2024
Cited by 3 | Viewed by 1713
Abstract
Baculoviruses are viral pathogens that infect different species of Lepidoptera, Diptera, and Hymenoptera, with a global distribution. Due to their biological characteristics and the biotechnological applications derived from these entities, the Baculoviridae family is an important subject of study and manipulation in the [...] Read more.
Baculoviruses are viral pathogens that infect different species of Lepidoptera, Diptera, and Hymenoptera, with a global distribution. Due to their biological characteristics and the biotechnological applications derived from these entities, the Baculoviridae family is an important subject of study and manipulation in the natural sciences. With the advent of RNA interference mechanisms, the presence of baculoviral genes that do not code for proteins but instead generate transcripts similar to microRNAs (miRNAs) has been described. These miRNAs are functionally associated with the regulation of gene expression, both in viral and host sequences. This article provides a comprehensive review of miRNA biogenesis, function, and characterization in general, with a specific focus on those identified in baculoviruses. Furthermore, it delves into the specific roles of baculoviral miRNAs in regulating viral and host genes and presents structural and thermodynamic stability studies that are useful for detecting shared characteristics with predictive utility. This review aims to expand our understanding of the baculoviral miRNAome, contributing to improvements in the production of baculovirus-based biopesticides, management of resistance phenomena in pests, enhancement of recombinant protein production systems, and development of diverse and improved BacMam vectors to meet biomedical demands. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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16 pages, 4040 KiB  
Review
CRISPR/dCas9 Tools: Epigenetic Mechanism and Application in Gene Transcriptional Regulation
by Ruijie Cai, Runyu Lv, Xin’e Shi, Gongshe Yang and Jianjun Jin
Int. J. Mol. Sci. 2023, 24(19), 14865; https://doi.org/10.3390/ijms241914865 - 3 Oct 2023
Cited by 20 | Viewed by 6981
Abstract
CRISPR/Cas9-mediated cleavage of DNA, which depends on the endonuclease activity of Cas9, has been widely used for gene editing due to its excellent programmability and specificity. However, the changes to the DNA sequence that are mediated by CRISPR/Cas9 affect the structures and stability [...] Read more.
CRISPR/Cas9-mediated cleavage of DNA, which depends on the endonuclease activity of Cas9, has been widely used for gene editing due to its excellent programmability and specificity. However, the changes to the DNA sequence that are mediated by CRISPR/Cas9 affect the structures and stability of the genome, which may affect the accuracy of results. Mutations in the RuvC and HNH regions of the Cas9 protein lead to the inactivation of Cas9 into dCas9 with no endonuclease activity. Despite the loss of endonuclease activity, dCas9 can still bind the DNA strand using guide RNA. Recently, proteins with active/inhibitory effects have been linked to the end of the dCas9 protein to form fusion proteins with transcriptional active/inhibitory effects, named CRISPRa and CRISPRi, respectively. These CRISPR tools mediate the transcription activity of protein-coding and non-coding genes by regulating the chromosomal modification states of target gene promoters, enhancers, and other functional elements. Here, we highlight the epigenetic mechanisms and applications of the common CRISPR/dCas9 tools, by which we hope to provide a reference for future related gene regulation, gene function, high-throughput target gene screening, and disease treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms of mRNA Transcriptional Regulation: 2nd Edition)
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