ZC3H12A/MCPIP1/Regnase-1-related endonucleases: An evolutionary perspective on molecular mechanisms and biological functions.

The mammalian Zc3h12a/MCPIP1/Regnase-1, an extensively studied regulator of inflammatory response, is the founding member of a ribonuclease family, which includes proteins related by the presence of the so-called Zc3h12a-like NYN domain. Recently, several related proteins have been described in Caenorhabditis elegans, allowing comparative evaluation of molecular functions and biological roles of these ribonucleases. We discuss the structural features of these proteins, which endow some members with ribonuclease (RNase) activity while others with auxiliary or RNA-independent functions. We also consider their RNA specificity and highlight a common role for these proteins in cellular defense, which is remarkable considering the evolutionary distance and fundamental differences in cellular defense mechanisms between mammals and nematodes.