A multifunctional protein EWS regulates the expression of Drosha and microRNAs

K. Y. Kim; Y. J. Hwang; M. K. Jung; J. Choe; Y. Kim; S. Kim; C. J. Lee; H. Ahn; J. Lee; N. W. Kowall; Y. K. Kim; J. I. Kim; S. B. Lee; H. Ryu

doi:10.1038/cdd.2013.144

A multifunctional protein EWS regulates the expression of Drosha and microRNAs

K. Y. Kim, Y. J. Hwang, M. K. Jung, J. Choe, Y. Kim, S. Kim, C. J. Lee, H. Ahn, J. Lee, N. W. Kowall, Y. K. Kim, J. I. Kim, S. B. Lee, H. Ryu

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35 Citations (Scopus)

Abstract

EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.

Original language	English
Pages (from-to)	136-145
Number of pages	10
Journal	Cell Death and Differentiation
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/cdd.2013.144
Publication status	Published - 2014 Jan

Bibliographical note

Funding Information:
Acknowledgements. We thank Dr. V Narry Kim for providing Drosha, DGCR8, and Dicer plasmids and Dr. Fukamizu for providing EWS plasmid. We also thank Elizabeth (Eun Kyung) Park (Boston University School of Medicine) for the preparation of manuscript. This study was supported by Brain Science Flagship Grant (2E24320) (HR) from Korea Institute of Science and Technology and NIH Grant (NS 067283-01A1) (HR).

Keywords

CTGF
Drosha
EWS
dermal development
microRNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/cdd.2013.144

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title = "A multifunctional protein EWS regulates the expression of Drosha and microRNAs",

abstract = "EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.",

keywords = "CTGF, Drosha, EWS, dermal development, microRNA",

author = "Kim, {K. Y.} and Hwang, {Y. J.} and Jung, {M. K.} and J. Choe and Y. Kim and S. Kim and Lee, {C. J.} and H. Ahn and J. Lee and Kowall, {N. W.} and Kim, {Y. K.} and Kim, {J. I.} and Lee, {S. B.} and H. Ryu",

note = "Funding Information: Acknowledgements. We thank Dr. V Narry Kim for providing Drosha, DGCR8, and Dicer plasmids and Dr. Fukamizu for providing EWS plasmid. We also thank Elizabeth (Eun Kyung) Park (Boston University School of Medicine) for the preparation of manuscript. This study was supported by Brain Science Flagship Grant (2E24320) (HR) from Korea Institute of Science and Technology and NIH Grant (NS 067283-01A1) (HR).",

year = "2014",

month = jan,

doi = "10.1038/cdd.2013.144",

language = "English",

volume = "21",

pages = "136--145",

journal = "Cell Death and Differentiation",

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T1 - A multifunctional protein EWS regulates the expression of Drosha and microRNAs

AU - Kim, K. Y.

AU - Hwang, Y. J.

AU - Jung, M. K.

AU - Choe, J.

AU - Kim, Y.

AU - Kim, S.

AU - Lee, C. J.

AU - Ahn, H.

AU - Lee, J.

AU - Kowall, N. W.

AU - Kim, Y. K.

AU - Kim, J. I.

AU - Lee, S. B.

AU - Ryu, H.

N1 - Funding Information: Acknowledgements. We thank Dr. V Narry Kim for providing Drosha, DGCR8, and Dicer plasmids and Dr. Fukamizu for providing EWS plasmid. We also thank Elizabeth (Eun Kyung) Park (Boston University School of Medicine) for the preparation of manuscript. This study was supported by Brain Science Flagship Grant (2E24320) (HR) from Korea Institute of Science and Technology and NIH Grant (NS 067283-01A1) (HR).

PY - 2014/1

Y1 - 2014/1

N2 - EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.

AB - EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.

KW - CTGF

KW - Drosha

KW - EWS

KW - dermal development

KW - microRNA

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DO - 10.1038/cdd.2013.144

M3 - Article

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SN - 1350-9047

VL - 21

SP - 136

EP - 145

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

IS - 1

ER -

A multifunctional protein EWS regulates the expression of Drosha and microRNAs

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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