About this Research Topic
Gene expression is essential to the proper growth and development of all organisms. A great challenge in molecular biology today is to precisely understand how genetic programs are established in eukaryotic cells in response to changes in the environment, namely how cells rapidly, coordinately and efficiently switch gene expression programs. In contrast to the situation in procaryotes, in eukaroytes the genetic material and the translation machinery are present in different cellular compartments. This implies that the cell must have established a means to communicate from the nucleus to the cytoplasm and vice-versa. Furthermore in eukaryotes genes that encode proteins, which function as multi-subunit complexes or which participate in the same function, are not organized in operons but instead are spread throughout the genome. This again means that somehow mRNAs need to be marked during synthesis in the nucleus for subsequent coordination of expression and/or function in the cytoplasm.
The Ccr4-Not complex is a multi-subunit complex that is conserved in all eukaryotes, is essential for yeast viability and for embryonic development in higher eukaryotes. In animal cells, mi-RNA-mediated silencing that contributes essentially to gene expression and health is mediated by recruitment of the Ccr4-Not complex to miRNA targets. It regulates all stages of the mRNA life cycle, from initiation of transcription in the nucleus to mRNA degradation in the cytoplasm. Consistently, single mutations in Ccr4-Not subunits have been correlated with opposite co-evolution of rates of mRNA synthesis and degradation in the eukaryotic kingdom. The complex is composed of 9 or more subunits and carries 2 enzymatic activities: deadenylation, the first and rate-limiting event in mRNA degradation and ubiquitination, a protein modification that can alter protein function or target proteins for degradation by the proteasome. Much evidence has accumulated to indicate that the Ccr4-Not complex is an essential component for coordination of gene expression between the nucleus and the cytoplasm in eukaryotic cells. Indeed, it is associated with transcribing ORFs and with translating ribosomes, and ubiquitination by the Ccr4-Not complex targets components of the transcription and translation machineries. Furthermore it is obviously an essential component of the RNA degradation machinery.
In this Research Topic, we will summarize and review the mechanistic, functional, structural and physiological information that has been clearly established for the Ccr4-Not complex. This will allow us to understand how this complex contributes to integrating different levels of gene expression in order to allow cells to efficiently, coordinately and unambiguously respond to the environment, and also to establish tissue-specific patterns of gene expression.
Through this research topic we would like to be able to define the challenges left to gain a thorough understanding of the implication of the Ccr4-Not complex in the coordinate regulation of gene expression in eukaryotic cells. Papers reviewing the evidence for the coordination of the different stages of gene expression in eukaryotes, papers relating the role of the Ccr4-Not complex in eukaryote physiology and in regulation of genes by miRNAs are encouraged.
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