SUMMARY Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population.

SUMMARY Translational readthrough, observed primarily in less complex organisms from viruses to Drosophila, expands the proteome by translating select transcripts beyond the canonical stop codon. Here we show that vascular endothelial growth factor-A (VEGFA) mRNA in mammalian endothelial cells undergoes programmed translational readthrough (PTR) generating VEGF-Ax, an isoform containing a unique 22-amino acid C-terminus extension. A cis-acting element in the VEGFA 3′UTR serves a dual function, not only encoding the appended peptide, but also directing the PTR by decoding the UGA stop codon as serine. Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 binds this element and promotes readthrough. Remarkably, VEGF-Ax exhibits anti-angiogenic activity in contrast to the pro-angiogenic activity of VEGF-A. Pathophysiological significance of VEGF-Ax is indicated by robust expression in multiple human tissues, but depletion in colon adenocarcinoma. Furthermore, genome-wide analysis revealed AGO1 and MTCH2 as authentic readthrough targets. Overall, our studies reveal a novel protein-regulated PTR event in a vertebrate system.

Nonlinear optical properties and carrier relaxation dynamics in graphene, suspended in three different solvents, are investigated using femtosecond (80 fs pulses) Z-scan and degenerate pumpprobe spectroscopy at 790 nm. The results demonstrate saturable absorption property of graphene with a nonlinear absorption coefficient, β, of ~2 to 9x10 -8 cm/W. Two distinct time scales associated with the relaxation of photoexcited carriers, a fast one in the range of 130-330 fs (related to carriercarrier scattering) followed by a slower one in 3.5-4.9 ps range (associated with carrier-phonon scattering) are observed.Graphene is a two-dimensional carbon nanomaterial which has received tremendous interest in recent years owing to its various remarkable properties and applications in modern electronics and photonics [1,2]. Ultrafast degenerate and nondegenerate pump-probe measurements on single and multilayer epitaxial [3,4] or exfoliated [5] graphenes deposited on a substrate have shown two types of dynamics of the carriers: a fast component of the order of ~100 fs attributed to the intraband carrier-carrier scattering and a slower component ~2 ps associated with carrierphonon scattering. In the degenerate pump-probe studies on single and multilayer graphene films grown on a SiC substrate using 85 fs laser pulses centered at 790 nm, a positive change in the transient differential transmission of the probe was observed with two relaxation times, the faster one in the range of 70-120 fs and a slower one between 0.4-1.7 ps [3]. Similar carrier relaxation dynamics was obtained in the nondegenerate pump-probe experiments on exfoliated graphene films on SiO 2 /Si substrate [5]. On a few layer thick graphene film on SiC, nondegenerate pump-probe experiments [4] using 800 nm pump showed that the sign of the differential transmission signal is positive over the entire probe spectral range of 1.1 to 2.6 µm but becomes negative after 2 ps if the probe wavelength falls between 1.78 and 2.35 µm. The initial positive part of the signal within 150 fs has been described in terms of thermalization and emission of high energy-phonons followed by a slow decay of the order of a few ps determined by electron-acoustic phonon scattering. Nonlinear optical properties of graphene have been reported recently in the nanosecond (ns) and picosecond (ps) regimes [6,7]. Using 35 ps laser pulses centered at 532 nm, it has been shown that the nonlinear response of graphene oxide suspensions changes from saturable absorption at low intensity (2.1 GW/cm 2 ) to reverse saturable absorption or optical limiting at higher intensities (>4.5 GW/cm 2 ) [6]. In comparison, in the ns regime suspensions of graphene oxide and functionalized graphene in dimethylformamide showed optical limiting property at all values of intensities above 0.6 GW/cm 2 [6,7].We have carried out femtosecond (80 fs) Z-scan and degenerate pump-probe experiments at 790 nm to study the nonlinear optical response and carrier dynamics in colloidal suspensions of graphene which have not been invest...

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Mechanisms that degrade inflammatory mRNAs are well-known, however stabilizing mechanisms are poorly understood. Here we show that Act1, an interleukin-17 (IL-17) receptor complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, SBE (SEFIR-binding element), in the inflammatory chemokine Cxcl1 3’ UTR. mRNA-bound Act1 directs formation of three compartmentally-distinct protein-RNA complexes (RNPs) that regulate three disparate events in inflammatory mRNA metabolism: preventing mRNA decay in the nucleus, inhibiting mRNA decapping in P-bodies, and promoting translation. SBE RNA aptamers reduced IL-17-mediated mRNA stabilization in vitro, IL-17-induced skin inflammation and airway inflammation in a mouse asthma model, providing a therapeutic strategy for autoimmune diseases. These results reveal a network in which Act1 assembles RNPs on the 3’ UTRs of select mRNAs to control receptor-mediated mRNA stabilization and translation during inflammation.