A new review brings to light the pivotal role of
ribonucleases (RNases) in shaping the molecular foundation of
Mendelian disorders. These essential enzymes, known for maintaining
RNA metabolism, are revealed as central players in a diverse spectrum of human diseases. When disrupted by genetic mutations, RNases lose their ability to regulate RNA dynamics, giving rise to
neurological,
growth-related,
hematopoietic, and
mitochondrial dysfunctions.
At the heart of these disorders are
loss-of-function mutations that compromise RNase activity either directly at the
catalytic core or through alterations in their
RNA recognition and
localization motifs. These defects are often associated with severe disease phenotypes, including
Aicardi-Goutières syndrome,
amyotrophic lateral sclerosis,
Perlman syndrome, and
progressive external ophthalmoplegia, among others. Many of the RNases involved in these disorders are
highly conserved across species, underscoring their fundamental biological importance.
The review explores how
small non-coding RNAs,
miRNAs,
piRNAs, and other RNA classes depend on RNase regulation for their biogenesis and turnover. In neurological diseases, the loss of RNase function disrupts
asymmetric neuronal translation, interferes with
immune surveillance, and hinders
RNA clearance mechanisms, leading to
neuroinflammation and
synaptic dysfunction. In growth disorders, mutations derail the
PI3K/AKT/mTOR signaling axis, promoting unregulated cell proliferation and
organ overgrowth. In the blood, RNase mutations impair
telomere maintenance and
ribosome maturation, compromising
hematopoietic stem cell renewal.
To bridge the gap between mutation and disease, the article highlights the indispensable value of
model organisms. Comparative studies across
mice,
zebrafish,
flies,
worms, and
yeast reveal conserved genetic pathways and provide critical insight into
disease pathogenesis. These models allow the functional dissection of mutations, mapping their consequences on
RNA stability,
protein synthesis, and
cellular stress responses. The availability of
single-cell transcriptomic atlases and
cross-species genetic tools accelerates the identification of candidate disease genes and the testing of
therapeutic strategies.
# # # # #
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 8.4
Impact Factor: 9.4
# # # # # #
More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available
online in
ScienceDirect (
https://www.sciencedirect.com/journal/genes-and-diseases ).
Submissions to
Genes & Disease may be made using
Editorial Manager (
https://www.editorialmanager.com/gendis/default.aspx ).
Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R
Contact Us: editor@genesndiseases.com
X (formerly Twitter): @GenesNDiseases (
https://x.com/GenesNDiseases )
# # # # # #
Reference
Annasha Dutta, Anastasiia Zaremba, Paulina Jackowiak, Ribonucleases in Mendelian disease: Characterization and insight from model organisms, Genes & Diseases, Volume 12, Issue 5, 2025, 101613,
https://doi.org/10.1016/j.gendis.2025.101613
Funding Information:
National Science Centre, Poland 2019/35/B/NZ2/02658