Cold Spring Harbor symposia on quantitative biology最新文献

The function of Dicer's helicase domain has been enigmatic since its discovery. Why do only some Dicers require ATP, despite a high degree of sequence conservation in their helicase domains? We discuss evolutionary considerations based on differences between vertebrate and invertebrate antiviral defense, and how the helicase domain has been co-opted in extant organisms as the binding site for accessory proteins. Many accessory proteins are double-stranded RNA binding proteins, and we propose models for how they modulate Dicer function and catalysis.

microRNAs (miRNAs) are crucial for posttranscriptional regulation of messenger RNAs. "Classical" miRNA targets predominantly interact with the miRNA seed sequence located near the miRNA 5' end. Interestingly, certain transcripts that exhibit extensive complementarity to the miRNAs 3' region, instead of being subjected to regulation, induce miRNA decay in a process termed target-directed miRNA degradation (TDMD). Here, we review recent advances in understanding the molecular mechanisms of TDMD. Specifically, we discuss how extensive miRNA complementarity to TDMD-inducing targets results in displacement of the miRNA 3' end from its protective pocket in the Argonaute protein. Unprotected miRNA 3' ends are then available for enzymatic attack by still-unidentified cellular enzymes. Identification of these cellular enzymes and discovery of additional TDMD-inducing transcripts are subjects for future research.

The fate of an RNA, from its localization, translation, and ultimate decay, is dictated by interactions with RNA binding proteins (RBPs). β-actin mRNA has functioned as the classic example of RNA localization in eukaryotic cells. Studies of β-actin mRNA over the past three decades have allowed understanding of how RBPs, such as ZBP1 (IGF2BP1), can control both RNA localization and translational status. Here, we summarize studies of β-actin mRNA and focus on how ZBP1 serves as a model for understanding interactions between RNA and their binding protein(s). Central to the study of RNA and RBPs were technological developments that occurred along the way. We conclude with a future outlook highlighting new technologies that may be used to address still unanswered questions about RBP-mediated regulation of mRNA during its life cycle, within the cell.

Alternative splicing is a pervasive gene regulatory mechanism utilized by both mammalian cells and viruses to expand their genomic coding capacity. The process of splicing and the RNA sequences that guide this process are the same in mammalian and viral transcripts; however, viruses lack the splicing machinery and therefore must usurp both the host spliceosome and many of the associated regulatory proteins in order to correctly process their genes. Here, we use the example of the influenza A virus to both describe how viruses utilize host splicing factors to regulate their own splicing and provide examples of how viral infection can, in turn, alter host splicing. Importantly, we show that at least some of the viral-induced changes in host splicing occur in genes that alter the efficiency of influenza replication. We emphasize the importance of increased understanding of the mechanistic interplay between host and viral splicing, and its functional consequences, in uncovering potential antiviral vulnerabilities.