ArticleProceedings of the National Academy of Sciences of the United States of America2014
MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- The transcriptome of early compensatory kidney growth reveals cell and time specific responses.iScience · 2024Article
- Dicer-Mediated mTORC1 Signaling and Parathyroid Gland Integrity and Function.Journal of the American Society of Nephrology : JASN · 2024Article
- 'Social' versus 'asocial' cells-dynamic competition flux balance analysis.NPJ systems biology and applications · 2023Article
- MicroRNA Expression Profile in TSC Cell Lines and the Impact of mTOR Inhibitor.International journal of molecular sciences · 2022Article
- Male infertility-associated Ccdc108 regulates multiciliogenesis via the intraflagellar transport machinery.EMBO reports · 2022Article
- Evaluation of Effective and Practical Euthanasia Methods for Larval African Clawed Frogs (Journal of the American Association for Laboratory Animal Science : JAALAS · 2020Article
- Modeling congenital kidney diseases inDisease models & mechanisms · 2019Review
- The Lhx1-Ldb1 complex interacts with Furry to regulate microRNA expression during pronephric kidney development.Scientific reports · 2018Article
- Polycystin 1 loss of function is directly linked to an imbalance in G-protein signaling in the kidney.Development (Cambridge, England) · 2018Article
- Article
- The Role of MicroRNAs in Cerebellar Development and Autism Spectrum Disorder During Embryogenesis.Molecular neurobiology · 2017Review
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Abnormal serum microRNA profiles in tuberous sclerosis are normalized during treatment with everolimus: possible clinical implications.Orphanet journal of rare diseases · 2016Article
- Regulation of PERK-eIF2α signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes.Nature communications · 2016Article
- Cortical Tubers: Windows into Dysregulation of Epilepsy Risk and Synaptic Signaling Genes by MicroRNAs.Cerebral cortex (New York, N.Y. : 1991) · 2016Article
- Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric kidney by modulating lipid rafts.Developmental biology · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
MicroRNAs (miRNAs) are major posttranscriptional regulators of a wide variety of biological processes. However, redundancy among most miRNAs has made it difficult to identify their in vivo functions. We previously demonstrated that global inhibition of miRNA biogenesis in Xenopus resulted in a dramatically smaller pronephric kidney. This suggested that microRNAs play a pivotal role in organ size control. Here we now provide a detailed mechanistic explanation for this phenotype. We identified that the activation of the mechanistic target of rapamycin complex 1 (mTORC1) by Insulin and insulin-like growth factor (Igf) 2 is an important regulator in kidney growth, which in turn is modulated by microRNAs. Molecular analyses demonstrate that microRNAs set a threshold for mTORC1 signaling by down-regulating one of its core negative regulators, tuberous sclerosis 1 (Tsc1). Most importantly, this rheostat can be reprogrammed experimentally. Whereas knockdown of miRNAs causes growth arrest, concomitant knockdown of Tsc1 restores mTORC1 activity and proximal tubular size. Together, these data establish a previously unidentified in vivo paradigm for the importance of posttranscriptional regulation in organ size control.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.