Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation

	Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation
	Salovska, Barbora 1,3; Zhu, Hongwen 2,4; Gandhi, Tejas 5; Frank, Max 6; Li, Wenxue 3; Rosenberger, George 7; Wu, Chongde 3; Germain, Pierre-Luc 8,9; Zhou, Hu 2,4; Hodny, Zdenek 1
刊名	MOLECULAR SYSTEMS BIOLOGY
	2020-03-01
卷号	16 期号:3 页码:19
关键词	alternative splicing DIA mass spectrometry protein turnover proteomics pulsed SILAC
ISSN号	1744-4292
通讯作者	Liu, Yansheng(yansheng.liu@yale.edu)
英文摘要	Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post-translational turnover, we devised a strategy combining pulse stable isotope-labeled amino acids in cells (pSILAC), data-independent acquisition mass spectrometry (DIA-MS), and a novel data analysis framework that resolves protein degradation rate on the level of mRNA alternative splicing isoforms and isoform groups. We demonstrated our approach by the genome-wide correlation analysis between mRNA amounts and protein degradation across different strains of HeLa cells that harbor a high grade of gene dosage variation. The dataset revealed that specific biological processes, cellular organelles, spatial compartments of organelles, and individual protein isoforms of the same genes could have distinctive degradation rate. The protein degradation diversity thus dissects the corresponding buffering or concerting protein turnover control across cancer cell lines. The data further indicate that specific mRNA splicing events such as intron retention significantly impact the protein abundance levels. Our findings support the tight association between transcriptome variability and proteostasis and provide a methodological foundation for studying functional protein degradation.
资助项目	Yale Cancer Systems Biology Symposium ; Czech Academy of Sciences[L200521953] ; Yale Cancer Center
WOS关键词	DATA-INDEPENDENT ACQUISITION ; DIFFERENTIAL EXPRESSION ; MASS-SPECTROMETRY ; TARGETED ANALYSIS ; INTRON RETENTION ; TURNOVER ; DYNAMICS ; IDENTIFICATION ; IMPACT ; QUANTIFICATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	WILEY
WOS记录号	WOS:000522453400002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280805]
专题	中国科学院上海药物研究所
通讯作者	Liu, Yansheng
作者单位	1.Czech Acad Sci, Inst Mol Genet, Dept Genome Integr, Prague, Czech Republic 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai, Peoples R China 3.Yale Univ, Yale Canc Biol Inst, West Haven, CT 06520 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 5.Biognosys, Zurich, Switzerland 6.European Mol Biol Lab, Heidelberg, Germany 7.Columbia Univ, Dept Syst Biol, New York, NY USA 8.Swiss Fed Inst Technol, D HEST, Inst Neurosci, Zurich, Switzerland 9.Univ Zurich, DMLS, Stat Bioinformat Lab, Zurich, Switzerland 10.Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA
推荐引用方式 GB/T 7714	Salovska, Barbora,Zhu, Hongwen,Gandhi, Tejas,et al. Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation[J]. MOLECULAR SYSTEMS BIOLOGY,2020,16(3):19.
APA	Salovska, Barbora.,Zhu, Hongwen.,Gandhi, Tejas.,Frank, Max.,Li, Wenxue.,...&Liu, Yansheng.(2020).Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation.MOLECULAR SYSTEMS BIOLOGY,16(3),19.
MLA	Salovska, Barbora,et al."Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation".MOLECULAR SYSTEMS BIOLOGY 16.3(2020):19.