Serganov, A. & Patel, D.J. Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. Nat. Rev. Genet. 8, 776-790

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature Reviews Genetics (Impact Factor: 36.98). 11/2007; 8(10):776-90. DOI: 10.1038/nrg2172
Source: PubMed


Although various functions of RNA are carried out in conjunction with proteins, some catalytic RNAs, or ribozymes, which contribute to a range of cellular processes, require little or no assistance from proteins. Furthermore, the discovery of metabolite-sensing riboswitches and other types of RNA sensors has revealed RNA-based mechanisms that cells use to regulate gene expression in response to internal and external changes. Structural studies have shown how these RNAs can carry out a range of functions. In addition, the contribution of ribozymes and riboswitches to gene expression is being revealed as far more widespread than was previously appreciated. These findings have implications for understanding how cellular functions might have evolved from RNA-based origins.

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    • "Riboswitches represent a common type of noncoding RNA that is present in the 5 0 UTRs of certain mRNAs (Serganov & Nudler, 2013). They offer important specialized components involved in the regulation of cellular function and operate through a conformational switch upon binding to a ligand (Barrick & Breaker, 2007; Breaker, 2012; Serganov & Patel, 2007). The regulatory mechanisms involved include, for example, formation or deletion of transcription terminator (Peselis & Serganov, 2012; Proshkin, Mironov, & Nudler, 2014), sequestration of ribosome-binding sites (Winkler & Breaker, 2005), and emergence of alternative cleavage sites (Cheah, Wachter, Sudarsan, & Breaker, 2007). "
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    ABSTRACT: The modular organization of RNA structure has been exploited in various computational and theoretical approaches to identify RNA tertiary (3D) motifs and assemble RNA structures. Riboswitches exemplify this modularity in terms of both structural and functional adaptability of RNA components. Here, we extend our computational approach based on tree graph sampling to the prediction of riboswitch topologies by defining additional edges to mimick pseudoknots. Starting from a secondary (2D) structure, we construct an initial graph deduced from predicted junction topologies by our data-mining algorithm RNAJAG trained on known RNAs; we sample these graphs in 3D space guided by knowledge-based statistical potentials derived from bending and torsion measures of internal loops as well as radii of gyration for known RNAs. We present graph sampling results for 10 representative riboswitches, 6 of them with pseudoknots, and compare our predictions to solved structures based on global and local RMSD measures. Our results indicate that the helical arrangements in riboswitches can be approximated using our combination of modified 3D tree graph representations for pseudoknots, junction prediction, graph moves, and scoring functions. Future challenges in the field of riboswitch prediction and design are also discussed. © 2015 Elsevier Inc. All rights reserved.
    Methods in enzymology 03/2015; 553C:115-135. DOI:10.1016/bs.mie.2014.10.054 · 2.09 Impact Factor
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    • "RNA is involved in processes like serving as a template and as an activated intermediate in protein synthesis along with being a ribosome component [9] [10] [11] [12]. RNA also participates in phenomenon like gene expression by catalyzing the maturation of mRNAs through ribozymes [13] [14] [15] [16] [17] and chromosome-end maintenance [18]. Disruption of any of these functions can have serious consequences on a cell. "
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    ABSTRACT: Vincristine and vinblastine are potent anti-proliferative compound whose mechanism of action inside a cell is not well elucidated and the basis of their differential cellular effect is also unknown. This work focuses towards understanding the interaction of vincristine and vinblastine with tRNA using spectroscopic approach. Fourier transform infrared (FTIR) spectroscopy, Fourier transform infrared difference spectroscopy and UV-visible spectroscopy were used to study the binding parameters of tRNA-alkaloids interaction. Both the vinca alkaloids interact with tRNA through external binding with some degree of intercalation into the nitrogenous bases. The alkaloids adduct formation did not alter the A-conformation of the biopolymer and vincristine-tRNA complexes were found to be more stable than that of vinblastine-tRNA complexes. The binding constants (K) estimated for VCR-tRNA and VBS-tRNA complexation are 3×10(2)M(-1) and 2.5×10(2)M(-1) respectively, which suggests low affinity of alkaloids to tRNA. The study recognizes tRNA binding properties of vital vinca alkaloids and contributes to a better understanding of their mechanism of action and could also help in identifying the reason behind their diverse action in a cell. Copyright © 2014 Elsevier B.V. All rights reserved.
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    • "RNA tertiary structures involve interactions between the secondary structure building blocks: for example, loop–stem, loop–loop and stem–stem interactions. RNA structures and functions are further diversified upon binding to proteins to form functional ribonucleoproteins such as snRNPs (11) and to other molecules and ions (as is the case in metabolite-sensing riboswitches) (1,7,8,10). Antisense therapeutics and microarray technologies (12–15) involve sequence-specific binding of oligonucleotides to single-stranded regions of target RNAs and have both had major impacts on biology and advancing RNA-based therapeutics. "
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