RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load

Poltronieri, Palmiro; Sun, Binlian; Mallardo, Massimo

miRNAs have become a prototype of several classes of small RNAs (sRNAs) [10] . These sRNAs act as single strand filaments incorporated into the RNA induced silencing complexes (RISC) acting as guides to Argonaute (Ago) enzymes degrading the target RNA complementary to these sRNAs. The processing into mature sRNAs requires protein complexes containing endoribonucleases: DROSHA in the nucleus, cleaving the dsRNA precursors into pre-miRNAs. The pre-miRNA hairpin structure is then exported into the cytoplasm via exportin-5. In the cytoplasm it assembles in RNA induced silencing complex (RISC) which includes Dicer ribonucleases that cleave pre-miRNAs into mature single strand sRNAs, Ago enzymes cleaving the mRNAs with sequences complementary to the microRNAs [11] , and other associated proteins, such as PW182/Argonaute-2, a 182 kDa RNAse associated to P-bodies [12] , HIV transactivating response RNA-binding protein (TRBP) [13] , and fragile X mental retardation protein (FMRP1) [14] . Mature miRNAs play important roles in the regulation of mammalian genes. It has been suggested that over 30% of all human genes are regulated by miRNAs. While recent genome-wide siRNA and shRNA screenings have shown that several hundred host cell proteins contribute to the regulation of HIV-1 infection in human cells, how miRNA-mediated regulation complements this picture is poorly understood. Other processing complexes are involved in the production of sRNA with various sizes: piwiRNA and siRNA, with size ranging from 21-nt to 25-nt, is the output of this processes. Their role is in the amplification of signals such as RNA primed RNA amplification, and the spreading of anti-viral RNA interference mechanism.