MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies

Diane Frankel (1, 2) , Valerie Delecourt (2) , Sophie Perrin (2) , Karim Harhouri (2) , Annachiara de Sandre-Giovannoli (2, 3) , Nicolas Lévy (2, 4) , Elise Kaspi (1, 2) , Patrice Roll (1, 2)

1 Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM]
2 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
3 CRB TAC - Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM]
4 Département de génétique médicale [Hôpital de la Timone - APHM]

Hereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue-specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson-Gil-ford progeria syndrome (HGPS) and other progeroid syndromes. MicroRNAs are small noncoding RNAs described as powerful regulators of gene expression, mainly by degrading target mRNAs or by inhibiting their translation. In recent years, the role of these small RNAs has become an object of study in laminopathies using in vitro or in vivo murine models as well as cells/tissues of patients. To date, few miRNAs have been reported to exert protective effects in laminopathies, including miR-9, which prevents progerin accumulation in HGPS neurons. The recent literature has described the potential implication of several other miRNAs in the patho-physiology of laminopathies, mostly by exerting deleterious effects. This review provides an overview of the current knowledge of the functional relevance and molecular insights of miRNAs in laminopathies. Furthermore, we discuss how these discoveries could help to better understand these diseases at the molecular level and could pave the way toward identifying new potential therapeutic targets and strategies based on miRNA modulation.

Mots clés: mRNAs; HGPS; HGPS-like; Hutchinson-Gilford progeria-like syndromes; hMSCs; human mesenchymal stem cells; hsa; Homo sapiens; IGF-1; insulin-like growth factor-1; INM; inner nuclear membrane; iPSCs; induced pluripotent stem cells; and leukomelanodermic papules; lncRNA; MAD; long-noncoding RNA; Mouse embryonic fibroblasts; Mandibuloacral dysplasia; miRNAs; MEFs; LGMD1B; limb-girdle muscular dystrophy type 1B; Nuclear pore complex; Nucleotides; ORF; open reading frame; RD; Restrictive dermopathy; Reactive oxygen species; ROS; VSMCs; Vascular smooth muscle cells dedifferentiation; ASCs; Acquired partial lipodystrophy; APLD; MicroRNA expression; Lamins; Laminopathies; Argonaute protein; AGO; adult-onset autosomal-dominant leukodystrophy; ADLD; Aging; Genetics; Hutchinson-Gilford progeria syndrome; nuclear envelope transmembrane partner proteins; NLS; NPC; Nuclear localization signal; ceRNA; Werner syndrome; AWS; Adipose stem cells; CMT2B1; congenital muscular dystrophy; competing endogenous RNA; CMD; DCM1A; Charcot-Marie-Tooth disease type 2B1; EDMD; Dilated cardiomyopathy type 1A; FPLD2; Dunnigan-type familial partial lipodystrophy; Emery-Dreifuss muscular dystrophy; Mmu; hepatitis C virus; HCV; Mus musculus; microRNAs; lamin-associated domains; LAD; hypertrophic cardiomyopathy; hepatic steatosis; LIRLLC; lipoatrophy with diabetes; NETs; Mesenchymal stem cells; Messenger RNAs; MSCs

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire; Génétique; Génétique humaine

Diane Frankel, Valerie Delecourt, Sophie Perrin, Karim Harhouri, Annachiara de Sandre-Giovannoli, et al.. MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies. Aging Cell, 2018, 17 (4), pp.e12766. ⟨10.1111/acel.12766⟩. ⟨hal-01925609⟩