l. High level of miR-222-3p was a mechanism for raloxifene resistance in EC therapy. Therefore, miR-222-3p could serve as potential therapeutic targets for a subset of ERa-negative ECs and might be developed as a biomarker for EC. Lassa fever virus has natural hosts in rodents and can cause severe and lethal hemorrhagic fever diseases in humans. The virus is estimated to infect 300,000 to 500,000 people annually and is responsible for 5,000 deaths per year in many endemic areas of West Africa. LASV is also a potential global heath threat as cases of infection have been reported in America, Europe and Asia. Currently, no vaccine is available to prevent LASV infections. The only drug available to treat LASV infection is ribavirin, but to be effective, it has to be administered early when the disease is insidious and therefore it is difficult to distinguish LASV infection from other febrile diseases. LASV belongs to the Arenaviridae family, which consists of enveloped viruses with a bisegmented single-stranded RNA genome. Using an ambisense coding strategy, LASV genome encodes four proteins: glycoprotein complex, nucleoprotein, matrix protein, and the L RNA-dependent RNA polymerase. The GPC is proteolytically cleaved by the cellular signal peptidase and subtilase SKI-1/S1P into a stable signal peptide SSP and mature glycoproteins GP1 and GP2. The SSP/GP1/GP2 tripartite complex forms surface envelope spikes of the virus and is anchored on the viral membrane. The highly abundant NP encapsulates viral RNAs into ribonucleoprotein complexes that also contain the L polymerase protein. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19643932 The NP-bound viral RNAs serve as templates for both RNA replication and transcription, which are facilitated by the L polymerase and NP proteins. In addition to its functions in viral RNP structural formation and genome transcription and replication, NP also strongly suppresses type I interferon production via a unique immune evasion mechanism. We and others have SAR 405 recently shown that NP has 3959 exoribonuclease activity with a preference for cleaving dsRNA substrates and that this viral exoribonuclease function is essential for mediating host immune suppression. A small matrix protein mediates viral budding and also regulates viral RNA replication and transcription. Like orthomyxoviruses and bunyaviruses, arenaviruses cannot synthesize de novo the cap structure that is required to initiate viral mRNA synthesis. Instead, these viruses steal the caps from host 1 Lassa Endonuclease Structure and Function mRNAs 
in a process termed cap snatching. Analysis of the nontemplated RNA sequences in virally infected cells suggests that the snatched cap structures in arenaviruses contain 1 to 4 ribonucleotide, which are much shorter than those of influenza and bunyaviruses. The cap snatching mechanism is most extensively studied in the influenza virus system. Influenza viral polymerase is a tripartite protein complex, which consists of the subunits PA, PB1, and PB2, each with specific functions in viral RNA replication and transcription. Structural analysis as well as biochemical and cell-based viral RNA synthesis assays demonstrate that PB2 binds the cap structure of host mRNAs while the N-terminal domain of the PA subunit endonucleolytically cleaves the cap structure from these mRNAs. In arenaviruses, mutagenesis studies have revealed that the Nterminal domain of the LASV L protein, which consists of 250 amino acid residues, is uniquely required for viral transcription but not