Post-transcriptional RNA regulons affecting cell cycle and proliferation

Abstract

The cellular growth cycle is initiated and maintained by punctual, yet agile, regulatory events involving modifications of cell cycle proteins as well as coordinated gene expression to support cyclic checkpoint decisions. Recent evidence indicates that post-transcriptional partitioning of messenger RNA subsets by RNA-binding proteins help physically localize, temporally coordinate, and efficiently translate cell cycle proteins. This dynamic organization of mRNAs encoding cell cycle components contributes to the overall economy of the cell cycle consistent with the post-transcriptional RNA regulon model of gene expression. This review examines several recent studies demonstrating the coordination of mRNA subsets encoding cell cycle proteins during nuclear export and subsequent coupling to protein synthesis, and discusses evidence for mRNA coordination of p53 targets and the DNA damage response pathway. We consider how these observations may connect to upstream and downstream post-transcriptional coordination and coupling of splicing, export, localization, and translation. Published examples from yeast, nematode, insect, and mammalian systems are discussed, and we consider genetic evidence supporting the conclusion that dysregulation of RNA regulons may promote pathogenic states of growth such as carcinogenesis.

A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

“…AU-rich elements or C-rich motifs; regulation of these RNAs is also exosome-dependent (Chen et al 2001;Mukherjee et al 2002;Keene 2007;Singer et al 2012;Blackinton and Keene 2014).…”

“…Exosomal degradation has roles in normal RNA biogenesis and turnover as well as surveillance of aberrant RNAs, including misfolded or mismodified tRNAs and mRNAs with defective polyadenylation (Allmang et al 1999;Kadaba 2004;Milligan et al 2005). The exosome has also been implicated in regulation of RNA regulons, functionally related sets of mRNAs that are tightly coregulated through common sequences in their 3 ′ untranslated regions (UTRs) (Chen et al 2001;Mukherjee et al 2002;Keene 2007;Singer et al 2012;Blackinton and Keene 2014).…”

HSP70-Ran-RCC1 transport system during cadmium-induced apoptosis in porcine kidney LLC-PK₁ cells

“…In this study, HSP70-Ran-RCC1 transport system was induced by cadmium exposure. The driving force of this transport system is the concentration gradient of Ran across the nuclear envelope (Blackinton and Keene, 2014), whose activation is initiated by induction of cytoplasmic HSP70. One of the roles of this transport system is to facilitate DNA repair; if the cellular damage is irreparable, apoptosis occurs.…”

Altered CELF1 binding to target transcripts in malignant T cells

“…Specific target sequences in mRNA can interact with RNA-binding proteins to coordinately regulate networks of transcripts involved in cell growth and development (Vlasova-St. Louis et al 2013) or other biological processes (Keene 2007;Blackinton and Keene 2014). A well-characterized example is the AU-rich element, which interacts with RNA-binding proteins to coordinate gene expression over the course of immune responses (Raghavan et al 2002;Ogilvie et al 2005Ogilvie et al , 2009Mukherjee et al 2009;VlasovaSt.…”