Non-coding RNAs at the Eukaryotic rDNA Locus: RNA–DNA Hybrids and Beyond
The human ribosomal DNA (rDNA) locus encodes a variety of long non-coding RNAs (lncRNAs). Among them, the canonical ribosomal RNAs that are the catalytic components of the ribosomes, as well as regulatory lncRNAs including promoter-associated RNAs (pRNA), stress-induced promoter and pre-rRNA antisense RNAs (PAPAS), and different intergenic spacer derived lncRNA species (IGSRNA). In addition, externally encoded lncRNAs are imported into the nucleolus, which orchestrate the complex regulation of the nucleolar state in normal and stress conditions via a plethora of molecular mechanisms. This review focuses on the triplex and R-loop formation aspects of lncRNAs at the rDNA locus in yeast and hu…
Skeletal muscle-specific methyltransferase METTL21C trimethylates p97 and regulates autophagy-associated protein breakdown
Summary: Protein aggregates and cytoplasmic vacuolization are major hallmarks of multisystem proteinopathies (MSPs) that lead to muscle weakness. Here, we identify METTL21C as a skeletal muscle-specific lysine methyltransferase. Insertion of a β-galactosidase cassette into the Mettl21c mouse locus revealed that METTL21C is specifically expressed in MYH7-positive skeletal muscle fibers. Ablation of the Mettl21c gene reduced endurance capacity and led to age-dependent accumulation of autophagic vacuoles in skeletal muscle. Denervation-induced muscle atrophy highlighted further impairments of autophagy-related proteins, including LC3, p62, and cathepsins, in Mettl21c−/− muscles. In addition, w…
Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.
Heart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein ki…