As a member of the vertebrate-specific secreted ribonucleases, angiogenin (ANG) was

As a member of the vertebrate-specific secreted ribonucleases, angiogenin (ANG) was first isolated and identified solely by its ability to induce new blood ship formation, and now, it has been recognized to play important functions in various physiological and pathological processes through regulating cell proliferation, survival, migration, invasion, and/or differentiation. alter the secondary structure or stability of ANG, but rather disrupt its ribonucleolytic activity or subcellular distribution [16,18]. This has stimulated interest in understanding the functions of ANG in the central nervous system, especially in neurodegenerative conditions, which may provide novel diagnostic methods and therapeutic targets. Here, we review the structure, mechanism, and functions of ANG reported over the past three decades. In addition, current questions and future directions regarding ANG research will also be discussed. By understanding ANG in a wide context, it may be possible to better delineate its functions in diseases. Basic Characteristics of ANG ANG gene arrangement The gene encoding ANG has been identified in nearly all vertebrates including fishes, reptiles, parrots, and mammals, but not in invertebrates [19C22] (Table?1). Analyses 918659-56-0 manufacture of complete or nearly complete mammalian genomes indicated the absence of ANG in Hepacam2 six mammalian species (gibbon, naked mole rat, guinea pig, doggie, giant panda, and African elephant) [23]. Notably, evolutionary and structural feature analyses showed that the ANG family evolves and duplicates from early genes [20]. To date, the mouse has been shown to possess the largest ANG family, including five mouse genes (pseudogenes (shows angiogenic activity and has the same structure as the human gene [25,26]. Table?1. Numbers of ANG genes and pseudogenes identified from complete or nearly complete genome sequences of vertebrates Comparable to 918659-56-0 manufacture all the other known ribonucleases (RNases), ANG is usually encoded by a single exon and is usually usually located in the middle of the RNase A superfamily gene cluster. Particularly, the human and mouse loci have a unique gene arrangement, characterized by shared promoters and 5-untranslated regions (5-UTR) directing two distinct exons encoding and (and is usually controlled by a universal promoter or a liver-specific promoter [26]. As the promoter is usually generally involved 918659-56-0 manufacture in regulation of mRNA transcription and the 5-UTR affects the translation efficiency, the expression levels of and are expected to be similar. Indeed, the tissue distribution and cellular localization or secretion of and are almost identical or highly similar in human, mouse, and cattle [26C30]. Results from our laboratory indicated that the transcription of these two genes is regulated by RNA polymerase III elements and a CCCTC binding factor (CTCF)-dependent intragenic chromatin loop [31]. This unique gene arrangement of and was proposed to ensure the coexpression of these two proteins, which regulates important biological events. Figure?1. Gene structure of angiogenin (and are indicated … The promoter sharing and conservation of the 5-UTR sequence between and are also observed in other mammalian species for which the whole-genome sequence is available (Fig.?1). Conservation of this genomic structure through evolution probably reflects a selection constraint to maintain coregulation of the two genes, which in turn suggests a functional relationship between these genes. Unlike ANG that has very low ribonucleolytic activity, RNASE4 is a very active endonuclease with high evolution conservation and unique uridine specificity [32]. However, the biological roles of RNASE4 are still largely unclear. Recent studies have shown that, similar to ANG, RNASE4 is able to protect against neuron degeneration through promotion of angiogenesis, neurogenesis, and neuronal survival under conditions of stress [33]. Our unpublished data indicated that RNASE4 possesses tumorigenic activity. These data suggested that the two genes may be functionally associated. It will be interesting to experimentally determine the biological functions and mechanisms of action of.

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