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Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation

Topoisomerases are crucial to solve DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3β (Top3β) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein deficient in Fragile X syndrome and known to regul...

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Autores principales: Xu, Dongyi, Shen, Weiping, Guo, Rong, Xue, Yutong, Peng, Wei, Sima, Jian, Yang, Jay, Sharov, Alexei, Srikantan, Subramanya, Yang, Jiandong, Fox, David, Qian, Yong, Martindale, Jennifer L., Piao, Yulan, Machamer, James, Joshi, Samit R., Mohanty, Subhasis, Shaw, Albert C., Lloyd, Thomas E., Brown, Grant W., Ko, Minoru S.H., Gorospe, Myriam, Zou, Sige, Wang, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853347/
https://www.ncbi.nlm.nih.gov/pubmed/23912945
http://dx.doi.org/10.1038/nn.3479
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author Xu, Dongyi
Shen, Weiping
Guo, Rong
Xue, Yutong
Peng, Wei
Sima, Jian
Yang, Jay
Sharov, Alexei
Srikantan, Subramanya
Yang, Jiandong
Fox, David
Qian, Yong
Martindale, Jennifer L.
Piao, Yulan
Machamer, James
Joshi, Samit R.
Mohanty, Subhasis
Shaw, Albert C.
Lloyd, Thomas E.
Brown, Grant W.
Ko, Minoru S.H.
Gorospe, Myriam
Zou, Sige
Wang, Weidong
author_facet Xu, Dongyi
Shen, Weiping
Guo, Rong
Xue, Yutong
Peng, Wei
Sima, Jian
Yang, Jay
Sharov, Alexei
Srikantan, Subramanya
Yang, Jiandong
Fox, David
Qian, Yong
Martindale, Jennifer L.
Piao, Yulan
Machamer, James
Joshi, Samit R.
Mohanty, Subhasis
Shaw, Albert C.
Lloyd, Thomas E.
Brown, Grant W.
Ko, Minoru S.H.
Gorospe, Myriam
Zou, Sige
Wang, Weidong
author_sort Xu, Dongyi
collection PubMed
description Topoisomerases are crucial to solve DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3β (Top3β) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein deficient in Fragile X syndrome and known to regulate translation of mRNAs important for neuronal function and autism. Notably, the FMRP-Top3β interaction is abolished by a disease-associated FMRP mutation, suggesting that Top3β may contribute to pathogenesis of mental disorders. Top3β binds multiple mRNAs encoded by genes with neuronal functions related to schizophrenia and autism. Expression of one such gene, ptk2/FAK, is reduced in neuromuscular junctions of Top3β mutant flies. Synapse formation is defective in Top3β mutant flies and mice, as observed in FMRP mutant animals. Our findings suggest that Top3β acts as an RNA topoisomerase and works with FMRP to promote expression of mRNAs critical for neurodevelopment and mental health.
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spelling pubmed-38533472014-03-01 Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation Xu, Dongyi Shen, Weiping Guo, Rong Xue, Yutong Peng, Wei Sima, Jian Yang, Jay Sharov, Alexei Srikantan, Subramanya Yang, Jiandong Fox, David Qian, Yong Martindale, Jennifer L. Piao, Yulan Machamer, James Joshi, Samit R. Mohanty, Subhasis Shaw, Albert C. Lloyd, Thomas E. Brown, Grant W. Ko, Minoru S.H. Gorospe, Myriam Zou, Sige Wang, Weidong Nat Neurosci Article Topoisomerases are crucial to solve DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3β (Top3β) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein deficient in Fragile X syndrome and known to regulate translation of mRNAs important for neuronal function and autism. Notably, the FMRP-Top3β interaction is abolished by a disease-associated FMRP mutation, suggesting that Top3β may contribute to pathogenesis of mental disorders. Top3β binds multiple mRNAs encoded by genes with neuronal functions related to schizophrenia and autism. Expression of one such gene, ptk2/FAK, is reduced in neuromuscular junctions of Top3β mutant flies. Synapse formation is defective in Top3β mutant flies and mice, as observed in FMRP mutant animals. Our findings suggest that Top3β acts as an RNA topoisomerase and works with FMRP to promote expression of mRNAs critical for neurodevelopment and mental health. 2013-08-04 2013-09 /pmc/articles/PMC3853347/ /pubmed/23912945 http://dx.doi.org/10.1038/nn.3479 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Xu, Dongyi
Shen, Weiping
Guo, Rong
Xue, Yutong
Peng, Wei
Sima, Jian
Yang, Jay
Sharov, Alexei
Srikantan, Subramanya
Yang, Jiandong
Fox, David
Qian, Yong
Martindale, Jennifer L.
Piao, Yulan
Machamer, James
Joshi, Samit R.
Mohanty, Subhasis
Shaw, Albert C.
Lloyd, Thomas E.
Brown, Grant W.
Ko, Minoru S.H.
Gorospe, Myriam
Zou, Sige
Wang, Weidong
Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation
title Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation
title_full Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation
title_fullStr Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation
title_full_unstemmed Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation
title_short Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation
title_sort top3β is an rna topoisomerase that works with fragile x syndrome protein to promote synapse formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853347/
https://www.ncbi.nlm.nih.gov/pubmed/23912945
http://dx.doi.org/10.1038/nn.3479
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