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PP1 interactome during heart failure development

ABSTRACT: The PP1 interactome plays a central role in HF pathogenesis and is dysregulated at the level of the R-subunits in the failing heart, resulting in differential phosphorylation status of proteins across different subcellular compartments.With the combination if immunoaffinity purification and mass spectrometry we were able to map the PP1 interactome in a mouse model with dilated cardiomyopaty, which is the most common form of primary cardiomyopaty leading to HF.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Heart, Hela Cell

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Eleonora Corradini

LAB HEAD: Albert J.R. Heck

PROVIDER: PXD004643 | Pride | 2018-04-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Lysates_HF_progression.zip	Other
	OR10_20150903_EC_PP1_IP_H_10.raw	Raw
	OR10_20150903_EC_PP1_IP_H_37.raw	Raw
	OR10_20150903_EC_PP1_IP_H_38.raw	Raw
	OR10_20150903_EC_PP1_IP_H_39.raw	Raw

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Project description:Accurate and comprehensive de novo transcriptome profiling in heart is a central issue to better understand cardiac physiology and diseases. Although significant progress has been made in genome-wide profiling for quantitative changes in cardiac gene expression, current knowledge offers limited insights to the total complexity in cardiac transcriptome at individual exon level. To develop more robust bioinformatic approaches to analyze high-throughput RNA sequencing (RNA-Seq) data, with the focus on the investigation of transcriptome complexity at individual exon and transcript levels. In addition to overall gene expression analysis, the methods developed in this study were used to analyze RNA-Seq data with respect to individual transcript isoforms, novel spliced exons, novel alternative terminal exons, novel transcript clusters (i.e., novel genes) and long non-coding RNA genes. We applied these approaches to RNA-Seq data obtained from mouse hearts following pressure-overload induced by trans-aortic constriction. Based on experimental validations, analyses of the features of the identified exons/transcripts, and expression analyses including previously published RNA-Seq data, we demonstrate that the methods are highly effective in detecting and quantifying individual exons and transcripts. Novel insights inferred from the examined aspects of the cardiac transcriptome open ways to further experimental investigations. Our work provided a comprehensive set of methods to analyze mouse cardiac transcriptome complexity at individual exon and transcript levels. Applications of the methods may infer important new insights to gene regulation in normal and disease hearts in terms of exon utilization and potential involvement of novel components of cardiac transcriptome. Left ventricular tissues were collected from C57BL/6 mice after 1 week (hypertrophy stage, HY) and 8 weeks post trans-aortic constriction (TAC) procedure (heart failure stage, HF), respectively, and their corresponding Sham controls (Sham-HY, Sham-HF). To conduct RNA-Seq analysis, total RNAs from six TAC and Sham-operated mice at the HY stage and four TAC and corresponding Sham mice at the HF stage were obtained.

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PP1 interactome during heart failure development

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