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Biomedicines
Special Issues
mRNA Metabolism in Health and Disease 2.0
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mRNA Metabolism in Health and Disease 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 15455

Special Issue Editor

Dr. Luísa Romão

E-Mail Website
Guest Editor
Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal
Interests: nonsense-mediated mRNA decay; mRNA translational control
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The eukaryotic gene expression pathway involves a number of interlinked steps, in which messenger RNAs (mRNAs) that code for proteins and noncoding RNAs are the key intermediates. In the nucleus, the mRNA precursor is transcribed from DNA and processed, and the mature mRNA is then exported to the cytoplasm, where it is translated into protein and finally degraded. In this process, mRNAs are associated with RNA-binding proteins forming messenger ribonucleoprotein (mRNP) complexes, whose protein content evolves throughout the lifetime of the mRNA. This mRNP assembly is important for all steps of the mRNA metabolism, and is of crucial importance for correct gene expression, which is necessary to maintain cellular homeostasis. In addition, during the complex life of mRNA, cells tightly control the quality and quantity of mRNAs using various surveillance pathways. Among these is nonsense-mediated mRNA decay, which detects and degrades mRNAs carrying premature translation-termination codons introduced through DNA mutations or pre-mRNA processing defects. Besides, exciting recent data have shown that cellular RNAs can be modified post-transcriptionally with dynamic and reversible chemical modifications. These modifications can alter the structure of mRNA, modulate different steps of mRNA metabolism, and control gene expression.

This Special Issue on "mRNA Metabolism in Health and Disease" aims to provide up-to-date insight into the remarkable complexity of the mRNA metabolism, as well as on its dysregulation in the context of many different human diseases, spanning from neurological, metabolic, and cardiovascular diseases to cancer.

Dr. Luísa Romão
Guest Editor

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Keywords

  • mRNA metabolism
  • transcription
  • RNA processing
  • mRNA export and localization
  • mRNA translation
  • mRNA surveillance
  • mRNA decay
  • mRNA modifications
  • gene expression regulation
  • human genetic disease
  • cancer

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Published Papers (3 papers)

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12 pages, 5784 KiB  
Article
The Binding Specificity of PAB1 with Poly(A) mRNA, Regulated by Its Structural Folding
by Monikaben Padariya and Umesh Kalathiya
Biomedicines 2022, 10(11), 2981; https://doi.org/10.3390/biomedicines10112981 - 19 Nov 2022
Viewed by 2264
Abstract
The poly(A)-binding protein cytoplasmic 1 (PAB1 or PABPC1) protein is associated with the long poly(A) mRNA tails, inducing stability. Herein, we investigated the dynamics of the PABPC1 protein, along with tracing its mRNA binding specificity. During molecular dynamics simulations (MDS), the R176-Y408 amino [...] Read more.
The poly(A)-binding protein cytoplasmic 1 (PAB1 or PABPC1) protein is associated with the long poly(A) mRNA tails, inducing stability. Herein, we investigated the dynamics of the PABPC1 protein, along with tracing its mRNA binding specificity. During molecular dynamics simulations (MDS), the R176-Y408 amino acids (RRM3–4 domains; RNA recognition motifs) initiated a folded structure that resulted in the formation of different conformations. The RRM4 domain formed high-frequency intramolecular interactions, despite such induced flexibility. Residues D45, Y54, Y56, N58, Q88, and N100 formed long-lasting interactions, and specifically, aromatic residues (Y14, Y54, Y56, W86, and Y140) gained a unique binding pattern with the poly(A) mRNA. In addition, the poly(A) mRNA motif assembled a PABPC1-specific conformation, by inducing movement of the center three nucleotides to face towards RRM1–2 domains. The majority of the high-frequency cancer mutations in PAB1 reside within the RRM4 domain and amino acids engaging in high-frequency interactions with poly(A) mRNA were found to be preserved in different cancer types. Except for the G123C variant, other studied cancer-derived mutants hindered the stability of the protein. Molecular details from this study will provide a detailed understanding of the PABPC1 structure, which can be used to modulate the activity of this gene, resulting in production of mutant peptide or neoantigens in cancer. Full article
(This article belongs to the Special Issue mRNA Metabolism in Health and Disease 2.0)
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Review

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12 pages, 1229 KiB  
Review
mRNA Metabolism and Hypertension
by Martina Zappa, Paolo Verdecchia, Antonio Spanevello, Michele Golino and Fabio Angeli
Biomedicines 2023, 11(1), 118; https://doi.org/10.3390/biomedicines11010118 - 3 Jan 2023
Viewed by 2280
Abstract
Hypertension is the most frequent cardiovascular risk factor all over the world. It remains a leading contributor to the risk of cardiovascular events and death. In the year 2015, about 1.5 billion of adult people worldwide had hypertension (as defined by office systolic [...] Read more.
Hypertension is the most frequent cardiovascular risk factor all over the world. It remains a leading contributor to the risk of cardiovascular events and death. In the year 2015, about 1.5 billion of adult people worldwide had hypertension (as defined by office systolic blood pressure ≥ 140 mmHg or office diastolic blood pressure ≥ 90 mmHg). Moreover, the number of hypertensive patients with age ranging from 30 to 79 years doubled in the last 30 years (from 317 million men and 331 million women in the year 1990 to 652 million men and 626 million women in 2019) despite stable age-standardized prevalence worldwide. Despite such impressive growth, the proportion of controlled hypertension is very low. A better understanding of the pathogenesis of hypertension may contribute to the development of innovative therapeutic strategies. In this context, alterations of the messenger RNA metabolism have been recently evaluated as contributors to the pathogenesis of hypertension, and pharmacological modulation of RNA metabolism is under investigation as potential and novel therapeutic armamentarium in hypertension. Full article
(This article belongs to the Special Issue mRNA Metabolism in Health and Disease 2.0)
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30 pages, 1351 KiB  
Review
Internal Ribosome Entry Site (IRES)-Mediated Translation and Its Potential for Novel mRNA-Based Therapy Development
by Rita Marques, Rafaela Lacerda and Luísa Romão
Biomedicines 2022, 10(8), 1865; https://doi.org/10.3390/biomedicines10081865 - 2 Aug 2022
Cited by 24 | Viewed by 10019
Abstract
Many conditions can benefit from RNA-based therapies, namely, those targeting internal ribosome entry sites (IRESs) and their regulatory proteins, the IRES trans-acting factors (ITAFs). IRES-mediated translation is an alternative mechanism of translation initiation, known for maintaining protein synthesis when canonical translation is [...] Read more.
Many conditions can benefit from RNA-based therapies, namely, those targeting internal ribosome entry sites (IRESs) and their regulatory proteins, the IRES trans-acting factors (ITAFs). IRES-mediated translation is an alternative mechanism of translation initiation, known for maintaining protein synthesis when canonical translation is impaired. During a stress response, it contributes to cell reprogramming and adaptation to the new environment. The relationship between IRESs and ITAFs with tumorigenesis and resistance to therapy has been studied in recent years, proposing new therapeutic targets and treatments. In addition, IRES-dependent translation initiation dysregulation is also related to neurological and cardiovascular diseases, muscular atrophies, or other syndromes. The participation of these structures in the development of such pathologies has been studied, yet to a far lesser extent than in cancer. Strategies involving the disruption of IRES–ITAF interactions or the modification of ITAF expression levels may be used with great impact in the development of new therapeutics. In this review, we aim to comprehend the current data on groups of human pathologies associated with IRES and/or ITAF dysregulation and their application in the designing of new therapeutic approaches using them as targets or tools. Thus, we wish to summarise the evidence in the field hoping to open new promising lines of investigation toward personalised treatments. Full article
(This article belongs to the Special Issue mRNA Metabolism in Health and Disease 2.0)
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