In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Question: Historically, research on RNA helicase and translocation enzymes has seemed like a footnote to the extraordinary progress in studies on DNA-remodeling enzymes. However, during the past decade, the rising wave of activity in RNA science has engendered intense interest in the behaviors of specialized motor enzymes that remodel RNA molecules. Functional, mechanistic, and structural investigations of these RNA enzymes have begun to reveal the molecular basis for their key roles in RNA metabolism and signaling. In this chapter, we highlight the structural and mechanistic similarities among monomeric RNA translo-case enzymes, while emphasizing the many divergent characteristics that have caused this enzyme family to become one of the most important in metabolism and gene expression.

Answer: Molecular Mechanics of RNA Translocases


Question: of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV. Coronaviruses are animal viruses containing an enveloped, positive-sense, single-stranded RNA genome; and include the common cold human coronavirus (CoV)-229E & CoV-OC43, severe acute respiratory syndrome (SARS) CoV, Middle East respiratory syndrome (MERS) CoV, porcine transmissible gastroenteritis virus (TGEV), and murine hepatitis virus (MHV) etc 1-3 . Since the 2003 SARS outbreak (which had a mortality rate of ~10%), novel anti-SARS-CoV treatments have been vigorously pursued. No new cases of SARS have been reported since the 2003 outbreak, but another novel coronavirus (MERS-CoV), this time with a mortality rate of ~35%, came to light in 2012 4 . To date, neither a commercially available vaccine for human coronaviruses nor a specific treatment for SARS-CoV or MERS-CoV is available. Coronaviruses primarily infect the upper respiratory and gastrointestinal tract and induce host inflammation 5 . Nuclear factor κB (NF-κB) activation by coronaviruses is usually responsible for mediating the production of pro-inflammatory cytokines and chemokines and thus plays an important role in the pathogenesis of disease caused by coronaviruses 6, 7 . Inhibition of NF-κB-mediated inflammation induced by coronavirus in mice was reported to increase the survival rate 6 . Thus, NF-κB inhibitors constitute a promising class of antivirals in infections caused by pathogenic coronaviruses. However, targeting NF-κB is limited by intrinsic pathway complexity, cross talk with other pathways, and drug resistance 8 . In addition, many small chemical molecules targeting either viral entry or the intracellular viral life cycle were reported to impart anti-coronavirus activity 2, 9, 10 . Despite these advances, however, SARS-CoV and MERS-CoV remain untreatable diseases for which novel therapies are sought. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 4105 | Tylophorine based compounds, whether isolated from plants, e.g. Asclepiadaceae and Moraceae or chemically synthesized, exert potent anti-coronaviral activities against a variety of coronaviruses including SARS-CoV, MHV, and TGEV 11, 12 , but both the underlying mechanism(s) of this inhibitory effect and the target are unknown. NF-κB is significantly activated after infection by coronaviruses, e.g. TGEV, and MHV etc 6, 7, [13] [14] [15] . Otherwise, coronaviral nucleocapsid (N) protein plays a vital role in the regulation of viral genome replication and host gene transcription 16 . Therefore, the combination treatment for the inhibition of coronavirus per se, e.g. viral genome replication, and blocking cellular NF-κB activation by coronaviruses, is a promising approach for the development of anti-coronavirals. TGEV infected swine testicular (ST) cells constitute a surrogate system for the search and study of potential anti-coronavirus agents 11, 12, 17 . Herein, we report: (1) tylophorine-based compounds exert potent anti-TGEV replication by directly targeting the viral RNA/ribonucleoprotein (RNP) complex for viral replication/synthesis; (2) NF-κB inhibition also leads to anti-TGEV replication; (3) A combination treatment consisting of both a tylophorine compound and an NF-κB inhibitor acts additively or synergically to more effectively and comprehensively inhibit TGEV replication than either (1) or (2) alone.

Answer: Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity OPEN


Question: Viruses are dependent on the cellular translation machinery for protein synthesis. Part of the innate immune response to infection is activation of the stress kinase PKR which phosphorylates the alpha subunit of the initiation factor eIF2. This results in inhibition of translation and is intended to block virus replication. A downstream effect of translational shutoff involves the formation of cytoplasmic granules, termed stress granules (SGs), that contain mRNAs, initiation factors, ribosomal subunits, and other mRNA regulatory proteins. SGs hold mRNAs in a translationally inactive state until cells recover from stress. Recent studies have begun to elucidate the impact of SGs on virus replication. Not surprisingly, viruses from diverse families have been found to modulate SG formation in infected cells by associating with important SG effecter proteins. This review describes the current knowledge on SGs and their interaction with and impact on virus replication. The most highly regulated stage of protein synthesis occurs at the initiation step. The translation initation factor eIF2 plays a crucial role in this process. In non-stressed cells, eIF2 complexed with GDP associates with eIF2B, a nucleotide exchange factor, which exchanges GDP for GTP. This exchange allows the eIF2:GTP complex to associate with initiator methionine tRNA to form ternary complex (eIF2:GTP:tRNA Met ). Ternary complex brings the initiating methionine to the 43S ribosome pre-initiation complex. The 43S complex contains the 40S ribosome and a variety of additional initiation factors that play important roles in translation. The 43S complex then forms the 48S ribosomal complex by binding mRNA, which has itself been activated for translation via association with additional initiation factors. The 60S ribosomal subunit is then recruited, at which point GTP is hydrolyzed to GDP and eIF2:GDP is released from the ribosomal complex to again associate with eIF2B and be recharged with GTP to start the process anew [reviewed in [1, 2] ]. Following cellular stress, the alpha subunit of eIF2 is phosphorylated by one of four stress activated kinases; GCN, which is activated during nutrient starvation, PERK, which is activated following ER stress, HRI, which is activated following oxidative stress and heme deficiency, and PKR, which is activated following virus infection [reviewed in [3] ].

Answer:
Stress Granules and Virus Replication HHS Public Access