Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses

BACKGROUND: Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses. RESULTS: Using a tagged-factor protein capture and RNA-sequencing (RNA-seq) approach, we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to three defined stresses that each cause a rapid attenuation of protein synthesis: oxidative stress induced by hydrogen peroxide and nutrient stresses caused by amino acid or glucose withdrawal. We find that acute stress leads to dynamic and unexpected changes in eIF4F-mRNA interactions that are shared among each factor and across the stresses imposed. eIF4F-mRNA interactions stabilised by stress are predominantly associated with translational repression, while more actively initiating mRNAs become relatively depleted for eIF4F. Simultaneously, other mRNAs are insulated from these stress-induced changes in eIF4F association. CONCLUSION: Dynamic eIF4F-mRNA interaction changes are part of a coordinated early translational control response shared across environmental stresses. Our data are compatible with a model where multiple mRNA closed-loop complexes form with differing stability. Hence, unexpectedly, in the absence of other stabilising factors, rapid translation initiation on mRNAs correlates with less stable eIF4F interactions

Molecular characterization and expression analysis of five different elongation factor 1 alpha genes in the flatfish Senegalese sole (Solea senegalensis Kaup): Differential gene expression and thyroid hormones dependence during metamorphosis

<p>Abstract</p> <p>Background</p> <p>Eukaryotic elongation factor 1 alpha (eEF1A) is one of the four subunits composing eukaryotic translation elongation factor 1. It catalyzes the binding of aminoacyl-tRNA to the A-site of the ribosome in a GTP-dependent manner during protein synthesis, although it also seems to play a role in other non-translational processes. Currently, little information is still available about its expression profile and regulation during flatfish metamorphosis. With regard to this, Senegalese sole (<it>Solea senegalensis</it>) is a commercially important flatfish in which <it>eEF1A </it>gene remains to be characterized.</p> <p>Results</p> <p>The development of large-scale genomics of Senegalese sole has facilitated the identification of five different <it>eEF1A </it>genes, referred to as <it>SseEF1A1</it>, <it>SseEF1A2</it>, <it>SseEF1A3</it>, <it>SseEF1A4</it>, and <it>Sse42Sp50</it>. Main characteristics and sequence identities with other fish and mammalian eEF1As are described. Phylogenetic and tissue expression analyses allowed for the identification of <it>SseEF1A1 </it>and <it>SseEF1A2 </it>as the Senegalese sole counterparts of mammalian <it>eEF1A1 </it>and <it>eEF1A2</it>, respectively, and of <it>Sse42Sp50 </it>as the ortholog of <it>Xenopus laevis </it>and teleost <it>42Sp50 </it>gene. The other two elongation factors, <it>SseEF1A3 </it>and <it>SseEF1A4</it>, represent novel genes that are mainly expressed in gills and skin. The expression profile of the five genes was also studied during larval development, revealing different behaviours. To study the possible regulation of <it>SseEF1A </it>gene expressions by thyroid hormones (THs), larvae were exposed to the goitrogen thiourea (TU). TU-treated larvae exhibited lower <it>SseEF1A4 </it>mRNA levels than untreated controls at both 11 and 15 days after treatment, whereas transcripts of the other four genes remained relatively unchanged. Moreover, addition of exogenous T4 hormone to TU-treated larvae increased significantly the steady-state levels of <it>SseEF1A4 </it>with respect to untreated controls, demonstrating that its expression is up-regulated by THs.</p> <p>Conclusion</p> <p>We have identified five different <it>eEF1A </it>genes in the Senegalese sole, referred to as <it>SseEF1A1</it>, <it>SseEF1A2</it>, <it>SseEF1A3</it>, <it>SseEF1A4</it>, and <it>Sse42Sp50</it>. The five genes exhibit different expression patterns in tissues and during larval development. TU and T4 treatments demonstrate that <it>SseEF1A4 </it>is up-regulated by THs, suggesting a role in the translational regulation of the factors involved in the dramatic changes that occurs during Senegalese sole metamorphosis.</p

Mammalian microRNA: an important modulator of host-pathogen interactions in human viral infections

MicroRNAs (miRNAs), which are small non-coding RNAs expressed by almost all metazoans, have key roles in the regulation of cell differentiation, organism development and gene expression. Thousands of miRNAs regulating approximately 60æ% of the total human genome have been identified. They regulate genetic expression either by direct cleavage or by translational repression of the target mRNAs recognized through partial complementary base pairing. The active and functional unit of miRNA is its complex with Argonaute proteins known as the microRNA-induced silencing complex (miRISC). De-regulated miRNA expression in the human cell may contribute to a diverse group of disorders including cancer, cardiovascular dysfunctions, liver damage, immunological dysfunction, metabolic syndromes and pathogenic infections. Current day studies have revealed that miRNAs are indeed a pivotal component of host-pathogen interactions and host immune responses toward microorganisms. miRNA is emerging as a tool for genetic study, therapeutic development and diagnosis for human pathogenic infections caused by viruses, bacteria, parasites and fungi. Many pathogens can exploit the host miRNA system for their own benefit such as surviving inside the host cell, replication, pathogenesis and bypassing some host immune barriers, while some express pathogen-encoded miRNA inside the host contributing to their replication, survival and/or latency. In this review, we discuss the role and significance of miRNA in relation to some pathogenic viruses

Does the Sun revolve around the Earth? A comparison between the general public and online survey respondents in basic scientific knowledge.

We conducted an online survey using a set of factual science questions that are commonly administered to assess fact-based scientific literacy. We report that the online population performed substantially better on this standard assessment than the traditional survey population. For example, it has been widely reported that 1 in 4 Americans does not know that the Earth revolves around the Sun, whereas among the online population, this ratio is reduced to 1 in 25. While new online platforms provide researchers with unprecedented ease of access to a large sample population for studying trends in public knowledge and attitudes, generalizing from online population samples to the US population at large poses a considerable challenge. We discuss the potential reasons for this discrepancy and the implications for conducting research online