Article

Coordinate regulation of mRNA decay networks by GU-rich elements and CELF1.

Department of Microbiology, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA.
Current opinion in genetics & development (Impact Factor: 8.99). 04/2011; 21(4):444-51. DOI: 10.1016/j.gde.2011.03.002
Source: PubMed

ABSTRACT The GU-rich element (GRE) was identified as a conserved sequence enriched in the 3' UTR of human transcripts that exhibited rapid mRNA turnover. In mammalian cells, binding to GREs by the protein CELF1 coordinates mRNA decay of networks of transcripts involved in cell growth, migration, and apoptosis. Depending on the context, GREs and CELF1 also regulate pre-mRNA splicing and translation. GREs are highly conserved throughout evolution and play important roles in the development of organisms ranging from worms to man. In humans, abnormal GRE-mediated regulation contributes to disease states and cancer. Thus, GREs and CELF proteins serve critical functions in gene expression regulation and define an important evolutionarily conserved posttranscriptional regulatory network.

0 Bookmarks
 · 
121 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: 4.5SI and 4.5SH are two non-coding RNAs about 100nt long, synthesized by RNA polymerase III in cells of various rodents including mice, rats, and hamsters. The first RNA is long-lived whereas the half-life of the second is only 20min. We previously found that the 16bp double-stranded structure (stem), formed by 4.5SI RNA termini, contributes essentially to the long lifetime of this RNA (Koval et al., 2012). The rapid decay of 4.5SH RNA seems to be related to the lack of a similar structure in this RNA. The aim of this work was to verify whether the lifetime of any other short-lived non-coding RNA can be prolonged following creation of the double-stranded structure with its terminal regions. Here RNAs transcribed by RNA polymerase III from short interspersed elements (SINEs) B2 and Rhin-1 from the genomes of mouse and horseshoe bat, respectively, were used. Replacement of 16nt at the 3'-terminal region by the sequence complementary to the 5' end region of B2 and Rhin-1 RNA increased their half-life more than 4 fold. In addition, we demonstrated that shortening of the terminal stem from 16 to 8bp decreased only slightly the 4.5SI RNA lifetime. Finally, we showed that the disruption of an internal (non-terminal) stem in 4.5SI RNA did not accelerate its decay in cells. Possible mechanisms of the small non-coding RNA lifetime extension are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.
    Gene 11/2014; DOI:10.1016/j.gene.2014.10.061 · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A large number of studies have shown the existence of metabolic covalent modifications in different molecular structures, able to store biochemical information that is not encoded by the DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in the self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by the specific input stimuli. The Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in the covalent post-translational modulation so that determined functional memory can be embedded in multiple stable molecular marks. Both the metabolic dynamics governed by Hopfield-type attractors (functional processes) and the enzymatic covalent modifications of determined molecules (structural dynamic processes) seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory). Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory) and an essentially conservative system (genetic memory). The molecular information of both systems seems to coordinate the physiological development of the whole cell.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Moderate leaf rolling is one of the most important morphological traits in rice breeding for plant ideotype. Previous studies have shown that the rl (t) gene has a high breeding potential for developing hybrid-rice varieties with an ideal ideotype, because it leads to an appropriate leaf rolling index (LRI) of about 30 % in the heterozygous state, and had a positive effect on grain yield. In this study, we isolated rl (t) and performed a preliminary investigation of its function in regulating leaf rolling in rice. DNA sequencing identified a single base change (G to T) in the finely mapped region (11 kb) containing rl (t), and this is located in 3′-untranslated region (3′-UTR) of the only predicted gene, Roc5 (Rice outermost cell-specific). The expression level of Roc5 is significantly higher in the rl (t) mutant than in the wild-type. Using RNAi and overexpression analysis, we found that the expression level of Roc5 correlated with LRI and leaf bulliform area, and was also associated with leaf abaxial or adaxial rolling. These results confirmed that Roc5 controls leaf rolling in a dosage-dependent manner. Bioinformatics analysis revealed a conserved 17-nt sequence (called the GU-rich element) in the 3′-UTR of HD-GL2 (Homeodomain-Glabra2) family genes including Roc5. Based on the model of this element in regulating mRNA stability in mammals, we speculate that the single nucleotide change in this element accounts for the higher expression level of Roc5 in the rl (t) mutant compared to the wild-type, which ultimately leads to adaxial rolling of the leaf. This discovery further enhances our knowledge of the molecular mechanisms underlying leaf rolling in rice.
    Chinese Science Bulletin 09/2014; 59(25). DOI:10.1007/s11434-014-0357-8 · 1.37 Impact Factor

Preview

Download
0 Downloads
Available from