Open Access
Open access
PLoS ONE, volume 15, issue 1, pages e0228160

The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells

Zhang Jinqiang 1
Han Chang 1
Song Kyoungsub 1
Chen Weina 1
Ungerleider Nathan 1
Yao Lu 1
Ma Wenbo 1
Wu Tong 1
1
 
Department of Pathology and Laboratory Medicine, Tulane, Wenbo University School of Medicine, New Orleans, Louisiana, United States of America
Publication typeJournal Article
Publication date2020-01-29
Journal: PLoS ONE
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor3.7
ISSN19326203
Multidisciplinary
Abstract
Recent studies have demonstrated the implication of long noncoding RNAs (lncRNAs) in a variety of physiological and pathological processes. However, the majority of lncRNAs are functionally unknown. The current study describes that the lncRNA MALAT1 regulates TGF-β/Smad signaling pathway through formation of a lncRNA-protein complex containing Smads, SETD2 and PPM1A. Our data show that this lncRNA-proteins complex facilitates the dephosphorylation of pSmad2/3 by providing the interaction niche for pSmad2/3 and their specific phosphatase PPM1A, thus terminating TGF-β/Smad signaling in hepatic cells. Based on these mechanistic studies, we performed further experiments to determine whether depletion of MALAT1 would augment cellular TGF-β/Smad signaling. We observed that MALAT1 depletion enhanced TGF-β/Smad signaling response, as reflect by amplification of Smad-mediated differentiation of induced pluripotent stem (iPS) cells to hepatocytes. Our experimental results demonstrate an important role of MALAT1 for regulation of TGF-β/Smad signaling in hepatic cells. Given the diverse functions of TGF-β/Smad pathway in various physiological and pathogenic processes, our results described in the current study will have broad implications for further understanding the role of MALAT1 in TGF-β/Smad pathway in human biology and disease.

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GOST Copy
Zhang J. et al. The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells // PLoS ONE. 2020. Vol. 15. No. 1. p. e0228160.
GOST all authors (up to 50) Copy
Zhang J., Han Chang, Song K., Chen W., Ungerleider N., Yao L., Ma W., Wu Tong The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells // PLoS ONE. 2020. Vol. 15. No. 1. p. e0228160.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1371/journal.pone.0228160
UR - https://doi.org/10.1371%2Fjournal.pone.0228160
TI - The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells
T2 - PLoS ONE
AU - Zhang, Jinqiang
AU - Han Chang
AU - Song, Kyoungsub
AU - Chen, Weina
AU - Ungerleider, Nathan
AU - Yao, Lu
AU - Ma, Wenbo
AU - Wu Tong
PY - 2020
DA - 2020/01/29 00:00:00
PB - Public Library of Science (PLoS)
SP - e0228160
IS - 1
VL - 15
PMID - 31995604
SN - 1932-6203
ER -
BibTex |
Cite this
BibTex Copy
@article{2020_Zhang,
author = {Jinqiang Zhang and Han Chang and Kyoungsub Song and Weina Chen and Nathan Ungerleider and Lu Yao and Wenbo Ma and Wu Tong},
title = {The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells},
journal = {PLoS ONE},
year = {2020},
volume = {15},
publisher = {Public Library of Science (PLoS)},
month = {jan},
url = {https://doi.org/10.1371%2Fjournal.pone.0228160},
number = {1},
pages = {e0228160},
doi = {10.1371/journal.pone.0228160}
}
MLA
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Zhang, Jinqiang, et al. “The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells.” PLoS ONE, vol. 15, no. 1, Jan. 2020, p. e0228160. https://doi.org/10.1371%2Fjournal.pone.0228160.
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