Mouse anti-Human DNM1 monoclonal antibody, clone 4H5C7

Adenosine deaminases acting on RNA 1 (ADAR1) catalyzes cellular RNA adenosine-to-inosine editing events on structured RNA molecules. In line with this critical role, ADAR1 exhibits ubiquitous expression and is essential for embryonic development. However, regulation and developmental significance of this RNA editor in a spatiotemporal context are largely elusive. Here we unveil a novel tissue-specific role of ADAR1 in skeletal myogenesis. ADAR1 expression displayed programmed alteration that is coordinated with differentiation cues, and mediated negatively by miRNA-1/206. Coincidently, ADAR1 exerts stage-dependent functions-suppression of apoptosis at the onset of differentiation and preservation of timely myotube formation through later phase. Furthermore, the post-transcriptional aspect of its myogenic role was illustrated by the spectrum of binding RNAs, as revealed by high-throughput approach, as well as by direct regulation of myogenesis-associated targets such as dynamin 1/2 (Dnm1/2) and annexin A4. Consequently, maintenance of target gene expression profiles likely contributes to a state of cytoskeleton and membrane dynamics that is amenable to myoblast morphogenesis. Collectively, these findings uncover a critical link of ADAR1 to myogenesis, and further highlight an epigenetic mechanism by which ADAR1 and miR-1/206 interplay to control scheduled myoblast-myotube transition.

The discovery that genetic mutations in several cellular pathways can increase lifespan has lent support to the notion that pharmacological inhibition of aging pathways can be used to extend lifespan and to slow the onset of age-related diseases. However, so far, only few compounds with such activities have been described. Here, we have conducted a chemical genetic screen for compounds that cause the extension of chronological lifespan of Schizosaccharomyces pombe. We have characterized eight natural products with such activities, which has allowed us to uncover so far unknown anti-aging pathways in S.pombe. The ionophores monensin and nigericin extended lifespan by affecting vacuolar acidification, and this effect depended on the presence of the vacuolar ATPase (V-ATPase) subunits Vma1 and Vma3. Furthermore, prostaglandin J(2) displayed anti-aging properties due to the inhibition of mitochondrial fission, and its effect on longevity required the mitochondrial fission protein Dnm1 as well as the G-protein-coupled glucose receptor Git3. Also, two compounds that inhibit guanosine monophosphate (GMP) synthesis, mycophenolic acid (MPA) and acivicin, caused lifespan extension, indicating that an imbalance in guanine nucleotide levels impinges upon longevity. We furthermore have identified diindolylmethane (DIM), tschimganine, and the compound mixture mangosteen as inhibiting aging. Taken together, these results reveal unanticipated anti-aging activities for several phytochemicals and open up opportunities for the development of novel anti-aging therapies.