• Something wrong with this record ?

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

B. Salovska, H. Zhu, T. Gandhi, M. Frank, W. Li, G. Rosenberger, C. Wu, PL. Germain, H. Zhou, Z. Hodny, L. Reiter, Y. Liu

. 2020 ; 16 (3) : e9170. [pub] -

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21012838
003      
CZ-PrNML
005      
20210507103627.0
007      
ta
008      
210420s2020 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.15252/msb.20199170 $2 doi
035    __
$a (PubMed)32175694
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Salovska, Barbora $u Yale Cancer Biology Institute, Yale University, West Haven, CT, USA $u Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
245    10
$a Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation / $c B. Salovska, H. Zhu, T. Gandhi, M. Frank, W. Li, G. Rosenberger, C. Wu, PL. Germain, H. Zhou, Z. Hodny, L. Reiter, Y. Liu
520    9_
$a 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.
650    _2
$a alternativní sestřih $7 D017398
650    _2
$a regulace genové exprese u nádorů $7 D015972
650    _2
$a HeLa buňky $7 D006367
650    _2
$a lidé $7 D006801
650    _2
$a izotopové značení $x metody $7 D007553
650    _2
$a hmotnostní spektrometrie $7 D013058
650    _2
$a protein - isoformy $x analýza $x metabolismus $7 D020033
650    _2
$a proteiny $x analýza $x metabolismus $7 D011506
650    _2
$a proteolýza $7 D059748
650    _2
$a proteomika $x metody $7 D040901
650    _2
$a izoformy RNA $x genetika $x metabolismus $7 D059368
650    _2
$a messenger RNA $x genetika $x metabolismus $7 D012333
650    _2
$a průběh práce $7 D057188
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Zhu, Hongwen $u Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
700    1_
$a Gandhi, Tejas $u Biognosys, Zurich-Schlieren, Switzerland
700    1_
$a Frank, Max $u European Molecular Biology Laboratory, Heidelberg, Germany
700    1_
$a Li, Wenxue $u Yale Cancer Biology Institute, Yale University, West Haven, CT, USA
700    1_
$a Rosenberger, George $u Department of Systems Biology, Columbia University, New York, NY, USA
700    1_
$a Wu, Chongde $u Yale Cancer Biology Institute, Yale University, West Haven, CT, USA
700    1_
$a Germain, Pierre-Luc $u Institute for Neuroscience, D-HEST, ETH Zurich, Zurich, Switzerland $u Statistical Bioinformatics Lab, DMLS, University of Zürich, Zurich, Switzerland
700    1_
$a Zhou, Hu $u Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
700    1_
$a Hodny, Zdenek $u Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Reiter, Lukas $u Biognosys, Zurich-Schlieren, Switzerland
700    1_
$a Liu, Yansheng $u Yale Cancer Biology Institute, Yale University, West Haven, CT, USA $u Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA
773    0_
$w MED00165996 $t Molecular systems biology $x 1744-4292 $g Roč. 16, č. 3 (2020), s. e9170
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32175694 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210420 $b ABA008
991    __
$a 20210507103626 $b ABA008
999    __
$a ok $b bmc $g 1651082 $s 1133217
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 16 $c 3 $d e9170 $e - $i 1744-4292 $m Molecular systems biology $n Mol Syst Biol $x MED00165996
LZP    __
$a Pubmed-20210420

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...