The cap-to-tail guide to mRNA turnover

Abstract

The levels of cellular messenger RNA transcripts can be regulated by controlling the rate at which the mRNA decays. Because decay rates affect the expression of specific genes, they provide a cell with flexibility in effecting rapid change. Moreover, many clinically relevant mRNAs--including several encoding cytokines, growth factors and proto-oncogenes--are regulated by differential RNA stability. But what are the sequence elements and factors that control the half-lives of mRNAs?

Anti-inflammatory functions of glucocorticoid-induced genes

“…The majority of these mRNAs have in common the presence of adenylate/uridylate-rich elements (AREs) in their 3' untranslated regions (UTRs). AREs form specific binding sites for ARE-binding proteins (AREBPs) such as tristetraprolin (TTP), which function by recruiting components of the cellular mRNA degradation machinery and causing rapid destruction of target mRNAs (Carrick et al, 2004;FengerGron et al, 2005;Guhaniyogi and Brewer, 2001;Kracht and Saklatvala, 2002;Lykke-Andersen and Wagner, 2005;Wilusz et al, 2001). ARE-AREBP complexes also mediate the post-transcriptional regulation of mRNA stability by signal transduction pathways.…”

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

“…However, ARE-directed turnover mechanisms are heterogeneous in rate of decay as well as in decay characteristics Wilusz et al, 2001). This heterogeneity presumably arises from the diverse RNA-binding factors recognizing the AREs and by the diverse RNA-protein and protein-protein interactions that regulate RNA turnover.…”

“…AUF1 is the most extensively characterized AREbinding protein, discussed in detail in earlier papers and reviews Wilusz et al, 2001). Briefly, AUF1 encodes for a family of four isoforms generated by alternative splicing denoted by their apparent molecular weights as p37 AUF1 , p40 AUF1 , p42 AUF1 , and p45 AUF1 (Wagner et al, 1998).…”

“…In mammals and in Xenopus, the Hu family consists of three members that are developmentally regulated and tissue-specific-Hel-N1 (also called HuB), HuC, and HuD-and one (HuR) that is ubiquitously expressed in all cell types (Szabo et al, 1991;King et al, 1994;Good, 1995;Ma et al, 1996;Antic and Keene, 1997). HuR is the best-characterized ELAV protein Brennan and Steitz, 2001;Wilusz et al, 2001). It has a high binding affinity for several AREs Good, 1997;Levy et al, 1998;Maurer et al, 1999;Sakai et al, 1999;Sokolowski et al, 1999), and although predominantly nuclear, it shuttles between the nucleus and the cytoplasm, affecting mRNA stability and translation (Fan and Steitz, 1998).…”

Posttranscriptional control of plant development

“…Once outside the nucleus, the CBC is replaced by eIF4E, which together with polyA-binding proteins stimulates the initiation of translation [7]. In addition, RNAs are subject to degradation by ribonucleases in both nuclear and cytoplasmic compartments [8,9].…”