Uncovering RNA binding proteins associated with age and gender during liver maturation

被引:8
作者
Chaturvedi, Praneet [1 ]
Neelamraju, Yaseswini [1 ]
Arif, Waqar [2 ]
Kalsotra, Auinash [2 ]
Janga, Sarath Chandra [1 ,3 ,4 ]
机构
[1] Indiana Univ Purdue Univ, Sch Informat & Comp, Dept BioHlth Informat, Indianapolis, IN 46202 USA
[2] Univ Illinois, Dept Biochem & Med Biochem, Urbana, IL 61801 USA
[3] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Hlth Informat & Translat Sci 5021, Indianapolis, IN 46202 USA
[4] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA
关键词
P53 TARGET WIG-1; GENE-EXPRESSION; SEX-DIFFERENCES; TRANSCRIPTOME; STABILITY; PROFILE; BLOOD;
D O I
10.1038/srep09512
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
In the present study, we perform an association analysis focusing on the expression changes of 1344 RNA Binding proteins (RBPs) as a function of age and gender in human liver. We identify 88 and 45 RBPs to be significantly associated with age and gender respectively. Experimental verification of several of the predicted associations in mice confirmed our findings. Our results suggest that a small fraction of the gender-associated RBPs (similar to 40%) are expressed higher in males than females. Altogether, these observations show that several of these RBPs are important and conserved regulators in maintaining liver function. Further analysis of the protein interaction network of RBPs associated with age and gender based on the centrality measures like degree, betweenness and closeness revealed that several of these RBPs might be prominent players in aging liver and impart gender specific alterations in gene expression via the formation of protein complexes. Indeed, both age and gender-associated RBPs in liver were found to show significantly higher clustering coefficients and network centrality measures compared to non-associated RBPs. The compendium of RBPs and this study will help us gain insight into the role of post-transcriptional regulatory molecules in aging and gender specific expression of genes.
引用
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页数:10
相关论文
共 45 条
[1]
The mRNA-Bound Proteome and Its Global Occupancy Profile on Protein-Coding Transcripts [J].
Baltz, Alexander G. ;
Munschauer, Mathias ;
Schwanhaeusser, Bjoern ;
Vasile, Alexandra ;
Murakawa, Yasuhiro ;
Schueler, Markus ;
Youngs, Noah ;
Penfold-Brown, Duncan ;
Drew, Kevin ;
Milek, Miha ;
Wyler, Emanuel ;
Bonneau, Richard ;
Selbach, Matthias ;
Dieterich, Christoph ;
Landthaler, Markus .
MOLECULAR CELL, 2012, 46 (05) :674-690
[2]
CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[3]
RNA binding proteins in the regulation of heart development [J].
Blech-Hermoni, Yotam ;
Ladd, Andrea N. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2013, 45 (11) :2467-2478
[4]
A faster algorithm for betweenness centrality [J].
Brandes, U .
JOURNAL OF MATHEMATICAL SOCIOLOGY, 2001, 25 (02) :163-177
[5]
Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface [J].
Buckberry, Sam ;
Bianco-Miotto, Tina ;
Bent, Stephen J. ;
Dekker, Gustaaf A. ;
Roberts, Claire T. .
MOLECULAR HUMAN REPRODUCTION, 2014, 20 (08) :810-819
[6]
System-wide identification of RNA-binding proteins by interactome capture [J].
Castello, Alfredo ;
Horos, Rastislav ;
Strein, Claudia ;
Fischer, Bernd ;
Eichelbaum, Katrin ;
Steinmetz, Lars M. ;
Krijgsveld, Jeroen ;
Hentze, Matthias W. .
NATURE PROTOCOLS, 2013, 8 (03) :491-500
[7]
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins [J].
Castello, Alfredo ;
Fischer, Bernd ;
Eichelbaum, Katrin ;
Horos, Rastislav ;
Beckmann, Benedikt M. ;
Strein, Claudia ;
Davey, Norman E. ;
Humphreys, David T. ;
Preiss, Thomas ;
Steinmetz, Lars M. ;
Krijgsveld, Jeroen ;
Hentze, Matthias W. .
CELL, 2012, 149 (06) :1393-1406
[8]
Genomic repertoires of DNA-binding transcription factors across the tree of life [J].
Charoensawan, Varodom ;
Wilson, Derek ;
Teichmann, Sarah A. .
NUCLEIC ACIDS RESEARCH, 2010, 38 (21) :7364-7377
[9]
RNA-binding proteins in early development [J].
Colegrove-Otero, LJ ;
Minshall, N ;
Standart, N .
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2005, 40 (01) :21-73
[10]
The Modern RNP World of Eukaryotes [J].
Collins, Lesley J. ;
Kurland, Charles G. ;
Biggs, Patrick ;
Penny, David .
JOURNAL OF HEREDITY, 2009, 100 (05) :597-604