Project description:Although several ribosomal protein (RP) paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes (RPL3L-ribosomes) in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide new insight into the mechanisms and physiological relevance of tissue-specific translational regulation.
Project description:Overall goal: To elucidate the function served by Rpl3L in heart. Purpose of analysis: To determine effects of Rpl3L-deficiency on translational mRNA profile in heart. Experimental structure: Polysomes and monosomes were fractionated from cardiac ventricles and associated RNA extracted for library generation and differential gene expression analyses between wild-type and Rpl3L-null samples, using standard RNAseq pipeline.
Project description:The ribosomal protein L3-like (RPL3L) is a striated muscle-specific ribosomal protein, and mutations in human RPL3L are linked with childhood cardiomyopathy and age-related atrial fibrillation. However, the function served by this protein, a paralogue of the ubiquitously expressed RPL3 protein, remains poorly characterized in both heart and skeletal muscle. To address this, null mutant mice with the Rpl3L gene deleted were generated and studied. The purpose of this microarray analyses was to compare transcriptional profiles of the null mutant hearts (lacking RPL3L) with wild-type control hearts (expressing RpL3L). We used microarrays to elucidate effects of Rpl3L deficiency on transcriptional profile of mouse hearts
Project description:RPL3L is a ribosomal protein expressed exclusively in adult straited muscle tissues, and a paralogue of the ubiquitously expressed RPL3. Here, we are looking into the effects of Rpl3l knockout on translation in adult mice hearts.
Project description:RPL3L is a ribosomal protein expressed exclusively in adult straited muscle tissues, and a paralogue of the ubiquitously expressed RPL3. Here, we are looking into the effects of Rpl3l knockout on translation in adult mice hearts.
Project description:Ribosome immunoprecipitates of cardiomyocytes isolated from Rpl3l-/- and Rpl3l+/+ mouse hearts were analysed using mass spectrometry.
Project description:The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes.
