PXD020566

PXD020566 is an original dataset announced via ProteomeXchange.

Title	Protein Identification and Post-translational Analysis of DMD and its associated Proteins in H19-proficient and -deficient Cells
Description	Dystrophin proteomic regulation in Muscular Dystrophies (MD) remains unclear. We report that a long noncoding RNA (lncRNA) H19 associates with dystrophin. To investigate the biological roles of this interaction in vivo, we performed mass spectrometry analysis of dystrophin and its associated proteins in H19-proficient and -deficient C2C12 myotubes. Mass spectrometry data indicated that in H19-proficient myotubes, dystrophin associates with components of dystrophin-associated protein complex (DPC); however, in H19-deficient myotubes, dystrophin associated with UBA1, UB2G1, TRIM63 ubiquitin E3 ligase and ubiquitin. In H19-deficient myotubes, dystrophin was post-translationally modified with K48-linked poly-ubiquitination at Lys3577 (referred to as Ub-DMD). This mass spectrometry study demonstrated that lncRNA H19, associates with dystrophin and inhibits E3 ligase-dependent Ub-DMD formation and its subsequent proteasomal degradation. Based on this study, H19 RNA oligonucleotides conjugated with a muscle homing ligand Agrin (referred to as AGR-H19) and Nifenazone, a TRIM63-specific small molecule inhibitor, reverses the dystrophin degradation in iPSC-derived skeletal muscle cells from Becker Muscular Dystrophy patients. Furthermore,treatment of mdx mice with exon-skipping reagent, in combination with either AGR-H19 or Nifenazone, dramatically stablized dystrophin, preserved skeletal/cardiac muscle histology, and improved strength/heart function. In summary, this mass spectrometry study paves the way to meaningful targeted therapeutics for BMD and certain DMD patients.
HostingRepository	PRIDE
AnnounceDate	2020-08-19
AnnouncementXML	Submission_2020-08-18_22:28:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liuqing Yang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-24 16:53:32	ID requested
⏵ 1	2020-08-18 22:28:02	announced

Dataset with its publication pending

submitter keyword: Mouse, C2C12, H19, Dystrophin, DMD, BMD, AGR-H19, Nifenazone, LC-MS

Liuqing Yang
contact affiliation	The University of Texas MD Anderson Cancer Center
contact email	lyang7@mdanderson.org
lab head
Liuqing Yang
contact affiliation	The University of Texas MD Anderson Cancer Center
contact email	lyang7@mdanderson.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020566
     1. Label: PRIDE project
     2. Name: Protein Identification and Post-translational Analysis of DMD and its associated Proteins in H19-proficient and -deficient Cells