MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that play their roles in the regulation of physiological and pathological processes. Originally, it was assumed that miRNAs only modulate gene expression posttranscriptionally in the cytoplasm by inducing target mRNA degradation. However, with further research, evidence shows that mature miRNAs also exist in the cell nucleus, where they can impact gene transcription and ncRNA maturation in several ways. This review provides an overview of novel models of nuclear miRNA functions. Some of the models remain to be verified by experimental evidence, and more details of the miRNA regulation network remain to be discovered in the future.
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http://dx.doi.org/10.3724/abbs.2023268 | DOI Listing |
Curr Opin Biotechnol
December 2024
Department of Life Sciences, Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. Electronic address:
The genetic code is a universally conserved mechanism that translates genetic information into proteins, consisting of 64 codons formed by four nucleotide bases. With a few exceptions, the genetic code universally encodes 20 canonical amino acids (AAs) and three stop signals, with many AAs represented by multiple codons. Genetic engineering has expanded this system through approaches like codon reassignment and synthetic base pair introduction, allowing for the incorporation of noncanonical AAs (ncAAs) into proteins, known as genetic code expansion (GCE).
View Article and Find Full Text PDFCell Death Differ
December 2024
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA.
View Article and Find Full Text PDFSci Rep
December 2024
Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, 90619-900, Brazil.
Tuberculosis remains a burden to this day, due to the rise of multi and extensively drug-resistant bacterial strains. The genome of Mycobacterium tuberculosis (Mtb) strain H37Rv underwent an annotation process that excluded small Open Reading Frames (smORFs), which encode a class of peptides and small proteins collectively known as microproteins. As a result, there is an overlooked part of its proteome that is a rich source of potentially essential, druggable molecular targets.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Orthopaedic Surgery, Keck School of Medicine, Stem Cell Research and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
Interleukin-6 (IL-6) is a major pro-inflammatory cytokine that demonstrates a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions.
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December 2024
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Targeting nuclear mechanics is emerging as a promising therapeutic strategy for sensitizing cancer cells to immunotherapy. Inhibition of the mechano-sensory kinase ATR leads to mechanical vulnerability of cancer cells, causing nuclear envelope softness and collapse and activation of the cGAS-STING-mediated innate immune response. Finding novel compounds that interfere with the non-canonical role of ATR in controlling nuclear mechanics presents an intriguing therapeutic opportunity.
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