Increased Cardiac Arrhythmogenesis Associated With Gap Junction Remodeling With Upregulation of RNA-Binding Protein FXR1.

Background: Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and posttranscriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins.

Regulation of Heart Rate in Drosophila via Fragile X Mental Retardation Protein.

RNA binding proteins play a pivotal role in post-transcriptional gene expression regulation, however little is understood about their role in cardiac function. The Fragile X (FraX) family of RNA binding proteins is most commonly studied in the context of neurological disorders, as mutations in Fragile X Mental Retardation 1 (FMR1) are the leading cause of inherited mental retardation. More recently, alterations in the levels of Fragile X Related 1 protein, FXR1, the predominant FraX member expressed in vertebrate striated muscle, have been linked to structural and functional defects in mice and zebrafish models.

Phosphorylation of tropomodulin1 contributes to the regulation of actin filament architecture in cardiac muscle.

Tropomodulin1 (Tmod1) is an actin-capping protein that plays an important role in actin filament pointed-end dynamics and length in striated muscle. No mechanisms have been identified to explain how Tmod1's functional properties are regulated. The purpose of this investigation was to explore the functional significance of the phosphorylation of Tmod1 at previously identified Thr54.