Reference - Detail
| RRC ID | 64806 |
|---|---|
| Author | Yatsuka H, Hada K, Shiraishi H, Umeda R, Morisaki I, Urushibata H, Shimizu N, Sebastian WA, Hikida T, Ishitani T, Hanada R, Shimada T, Kimoto K, Kubota T, Hanada T. |
| Title | Exosc2 deficiency leads to developmental disorders by causing a nucleotide pool imbalance in zebrafish. |
| Journal | Biochem Biophys Res Commun |
| Abstract |
Exosc2 is one of the components of the exosome complex involved in RNA 3' end processing and degradation of various RNAs. Recently, EXOSC2 mutation has been reported in German families presenting short stature, hearing loss, retinitis pigmentosa, and premature aging. However, the in vivo function of EXOSC2 has been elusive. Herein, we generated Exosc2 knockout (exosc2-/-) zebrafish that showed larval lethality 13 days post fertilization, with microcephaly, loss of spinal motor neurons, myelin deficiency, and retinitis pigmentosa. Mechanistically, Exosc2 deficiency caused impaired mRNA turnover, resulting in a nucleotide pool imbalance. Rapamycin, which modulated mRNA turnover by inhibiting the mTOR pathway, improved nucleotide pool imbalance in exosc2-/- zebrafish, resulting in prolonged survival and partial rescue of neuronal defects. Taken together, our findings offer new insights into the disease pathogenesis caused by Exosc2 deficiency, and might help explain fundamental molecular mechanisms in neuronal diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. |
| Volume | 533(4) |
| Pages | 1470-1476 |
| Published | 2020-12-17 |
| DOI | 10.1016/j.bbrc.2020.10.044 |
| PII | S0006-291X(20)31961-6 |
| PMID | 33333712 |
| MeSH | Animals Animals, Genetically Modified CRISPR-Cas Systems Embryo, Nonmammalian / abnormalities Gene Expression Regulation, Developmental Gene Knockout Techniques Larva / genetics Larva / physiology Motor Neurons / drug effects Motor Neurons / pathology Myelin Basic Protein / genetics Nucleotides / genetics Nucleotides / metabolism* Sirolimus / pharmacology Zebrafish / embryology Zebrafish / genetics* |
| IF | 2.985 |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Zebrafish | Tg(isl1:GFP)rw0 |