Emerging role of angiogenin in stress response and cell survival under adverse conditions

Angiogenin (ANG), also known as ribonuclease (RNASE) 5, is a member of the vertebrate-specific, secreted RNASE superfamily. ANG was originally identified as a tumor angiogenic factor, but its biological activity has been extended from inducing angiogenesis to stimulating cell proliferation and more recently, to promoting cell survival. Under growth conditions, ANG is translocated to nucleus where it accumulates in nucleolus and stimulates ribosomal RNA (rRNA) transcription, thus facilitating cell growth and proliferation. Under stress conditions, ANG is accumulated in cytoplasmic compartments and modulates the production of tiRNA, a novel class of small RNA that is derived from tRNA and is induced by stress. tiRNA suppress global protein translation by inhibiting both cap-dependent and -independent translation including that mediated by weak IRESes. However, strong IRES-mediated translation, a mechanism often used by genes involved in pro-survival and anti-apoptosis, is not affected. Thus, ANG-mediated tiRNA reprogram protein translation, save anabolic energy, and promote cell survival. This recently uncovered function of ANG presents a novel mechanism of action in regulating cell growth and survival.