Altered nucleocytoplasmic proteome and transcriptome distributions in anin vitro model of amyotrophic lateral sclerosis

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474463.do
DOI
10.1371/journal.pone.0176462
Title
Altered nucleocytoplasmic proteome and transcriptome distributions in anin vitro model of amyotrophic lateral sclerosis
Description
This study was supported by Grants from the SK Telecom Research Fund(34-2013-0120) and from the Korea Healthcare Technology R&D project,Ministry of health and Welfare, Republic of Korea (HI14C3347). Thefunder provided support in the form of salaries for one of the authors[JHJ], but did not have any additional role in the study design, datacollection and analysis, decision to publish, or preparation of themanuscript.; This study was supported by Grants from the SK TelecomResearch Fund (34-2013-0120) and from the Korea Healthcare TechnologyR&D project, Ministry of health and Welfare, Republic of Korea(HI14C3347).; There is no any conflict of interest with this study. Oneof the authors [JHJ] is an employee of commercial company (MacrogenInc). The Macrogen provided support in the form of salaries for [JHJ],but did not have any additional role in the study design, datacollection and analysis, decision to publish, or preparation of themanuscript.
abstract
Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurode-generative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS. After subcellular fractionation of motor neuron-like cell lines expressing wild-type or G93A mutant hSOD1, quantitative mass spectrometry and next-generation RNA sequencing (RNA-seq) were performed for the nuclear and cytoplasmic compartments. A subset of the results was validated via immunoblotting. A total of 1,925 proteins were identified in either the nuclear or cytoplasmic fractions, and 32% of these proteins were quantified in both fractions. The nucleocytoplasmic distribution of 37 proteins was significantly changed in mutant cells with nuclear and cytoplasmic shifts in 13 and 24 proteins, respectively (p<0.05). The proteins shifted towards the nucleus were enriched regarding pathways of RNA transport and processing (Dhx9, Fmr1, Srsf3, Srsf6, Tra2b), whereas protein folding (Cct5, Cct7, Cct8), aminoacyl-tRNA biosynthesis (Farsb, Nars, Txnrd1), synaptic vesicle cycle (Cltc, Nsf), Wnt signalling (Cltc, Plcb3, Plec, Psmd3, Ruvbl1) and Hippo signalling (Camk2d, Plcb3, Ruvbl1) pathways were over-represented in the proteins shifted to the cytoplasm. A weak correlation between the changes in protein and mRNA levels was found only in the nucleus, where mRNA was relatively abundant in mutant cells. This study provides a comprehensive dataset of the nucleocytoplasmic distribution of the proteome and transcriptome in an in vitro model of ALS. An integrated analysis of the nucleocytoplasmic distribution of the proteome and transcriptome demonstrated multiple candi
provenance
Made available in Cube on 2018-09-28T10:46:44Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Jee-Eun
Hong, Yoon Ho
Kim, Jin Young
Jeon, Gye Sun
Jung, Jung Hee
Yoon, Byung-Nam
Son, Sung-Yeon
Lee, Kwang-Woo
Kim, Jong-Il
Sung, Jung-Joon
orcid
KIM, JONG-IL/0000-0002-7240-3744
accessioned
2018-09-28T10:46:44Z
available
2018-09-28T10:46:44Z
issued
2017
citation
PLOS ONE(12): 4
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474463.do
Funder
과학기술정보통신부
Funding Program
한국기초과학지원연구원연구운영비지원
Project ID
1711063462
Jurisdiction
Rep.of Korea
Project Name
Creative Basic Research
rights
openAccess
type
article


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