Current Opinion in Genetics & Development最新文献

Understanding the cellular and molecular determinants of mammalian tissue regeneration and repair is crucial for developing effective therapies that restore tissue architecture and function. In this review, we focus on the cell types involved in scarless wound response and regeneration of spiny mice (Acomys). Comparative -omics approaches with scar-prone mammals have revealed species-specific peculiarities in cellular behavior during the divergent healing trajectories. We discuss the developing views on which cell types engage in restoring the architecture of spiny mouse tissues through a co-ordinated spatiotemporal response to injury. While yet at the beginning of understanding how cells interact in these fascinating animals to regenerate tissues, spiny mice hold great promise for scar prevention and anti-fibrotic treatments.

Epitranscriptomic modification of tRNA has recently gained traction in the field of cancer biology. The presence of such modifications on tRNA appears to allow for translational control of processes central to progression and malignant transformation. Methyltransferase Like 1 protein (METTL1), along with other epitranscriptomic writers (e.g. NSUN3, NAT10, ELP3, etc.), has recently been investigated in multiple cancer types. Here, we review the impact of such tRNA modifications in tumorigenesis and the progression of cancer toward drug resistance and metastasis. Regulation of central cellular processes relied upon by malignant cancer cells through modulation of the tRNA epitranscriptome represents an area with great potential to bring novel first-in-class therapies to the clinic.

Altered RNA modification patterns and dysregulated expression of epitranscriptomic machinery proteins (EMPs) have been causatively correlated with several diseases. Modulation of EMP gene expression has shown promise in reversing disease-associated phenotypes, making EMPs attractive therapeutic targets.

Various therapeutic strategies, including small-molecule modulators, proteolysis-targeting chimeras, and molecular tools for site-specific engineering of RNA modifications, have been introduced to modulate EMPs and RNA modifications themselves and are currently being investigated to enrich the physician’s armamentarium. At the forefront of research are small-molecule inhibitors of the key players involved in the N⁶-methyladenosine RNA modification, with an inhibitor of methyltransferase 3 in clinical trials. Preclinical studies have also demonstrated proof-of-concept for the other approaches, raising expectations for this exciting new frontier of therapy.

N⁶-methyladenosine (m⁶A) is the most abundant internal modification of mRNAs in eukaryotes. Numerous studies have shown that m⁶A plays key roles in many biological and pathophysiological processes, including fertility. The factors involved in m⁶A-dependent mRNA regulation include writers, which deposit the m⁶A mark, erasers, which remove it, and readers, which bind to m⁶A-modified transcripts and mediate the regulation of mRNA fate. Many of these proteins are highly expressed in the germ cells of mammals, and some have been linked to fertility disorders in human patients. In this review, we summarise recent findings on the important roles played by proteins involved in m⁶A biology in mammalian gametogenesis and fertility. Continued study of the m⁶A pathway in the mammalian germline will shed further light on the importance of epitranscriptomics in reproduction and may lead to effective treatment of human fertility disorders.

The RNA modification of N⁶-methyladenosine (m⁶A) controls many aspects of RNA function that impact biological processes, including viral infection. In this review, we highlight recent work that shapes our current understanding of the diverse mechanisms by which m⁶A can regulate viral infection by acting on viral or cellular mRNA molecules. We focus on emerging concepts and understanding, including how viral infection alters the localization and function of m⁶A machinery proteins, how m⁶A regulates antiviral innate immunity, and the multiple roles of m⁶A in regulating specific viral infections. We also summarize the recent studies on m⁶A during SARS-CoV-2 infection, focusing on points of convergence and divergence. Ultimately, this review provides a snapshot of the latest research on m⁶A during viral infection.

Tissue homeostasis is intricately linked to cellular metabolism and metabolite exchange within the tissue microenvironment. The orchestration of adaptive cellular responses during injury and repair depends critically upon metabolic adaptation. This adaptation, in turn, shapes cell fate decisions required for the restoration of tissue homeostasis. Understanding the nuances of metabolic processes within the tissue context and comprehending the intricate communication between cells is therefore imperative for unraveling the complexity of tissue homeostasis and the processes of injury and repair. In this review, we focus on mass spectrometry imaging as an advanced platform with the potential to provide such comprehensive insights into the metabolic instruction governing tissue function. Recent advances in this technology allow to decipher the intricate metabolic networks that determine cellular behavior in the context of tissue resilience, injury, and repair. These insights not only advance our fundamental understanding of tissue biology but also hold implications for therapeutic interventions by targeting metabolic pathways critical for maintaining tissue homeostasis.

N⁶-methyladenosine (m⁶A) is the most abundant modification to mRNAs. Loss-of-function studies of main m⁶A regulators have indicated the role of m⁶A in pre-mRNA splicing. Recent studies have reported the role of splicing in preventing m⁶A deposition. Understanding the interplay between m⁶A and mRNA splicing holds the potential to clarify the significance of these fundamental molecular mechanisms in cell development and function, thereby shedding light on their involvement in the pathogenesis of myriad diseases.

Pseudouridine (Ψ), the most abundant RNA modification, plays a role in pre-mRNA splicing, RNA stability, protein translation efficiency, and cellular responses to environmental stress. Dysregulation of pseudouridylation is linked to human diseases. This review explores recent insights into the role of RNA pseudouridylation alterations in human disorders and the therapeutic potential of Ψ. We discuss the impact of the reduction of Ψ levels in ribosomal, messenger, and transfer RNA in RNA processing, protein translation, and consequently its role in neurodevelopmental diseases and cancer. Furthermore, we review the success of N1-methyl-Ψ messenger RNA vaccines against COVID-19 and the development of RNA-guided pseudouridylation enzymes for treating genetic diseases caused by premature stop codons.

Epitranscriptomics, the study of reversible and dynamic chemical marks on the RNA, is rapidly emerging as a pivotal field in post-transcriptional gene expression regulation. Increasing knowledge about epitranscriptomic landscapes implicated in disease pathogenesis proves an invaluable opportunity for the identification of epitranscriptomic biomarkers and the development of new potential therapeutic drugs. Hence, recent advances in the characterization of these marks and associated enzymes in both health and disease blaze a trail toward the use of epitranscriptomics approaches for clinical applications. Here, we review the latest studies to provide a wide and comprehensive perspective of clinical epitranscriptomics and emphasize its transformative potential in shaping future health care paradigms.