A single amino acid substitution in ORF1 dramatically decreases L1 retrotransposition and provides insight into nucleic acid chaperone activity

L1 is a ubiquitous interspersed repeated sequence in mammals that achieved its high copy number by autonomous retrotransposition. Individual L1 elements within a genome differ in sequence and retrotransposition activity. Retrotransposition requires two L1-encoded proteins, ORF1p and ORF2p. Chimeric elements were used to map a 15-fold difference in retrotransposition efficiency between two L1 variants from the mouse genome, TFC and TFspa, to a single amino acid substitution in ORF1p, D159H. The steady-state levels of L1 RNA and protein do not differ significantly between these two elements, yet new insertions are detected earlier and at higher frequency in TFC, indicating that it converts expressed L1 intermediates more effectively into new insertions. The two ORF1 proteins were purified and their nucleic acid binding and chaperone activities were examined in vitro. Although the RNA and DNA oligonucleotide binding affinities of these two ORF1 proteins were largely indistinguishable, D159 was significantly more effective as a nucleic acid chaperone than H159. These findings support a requirement for ORF1p nucleic acid chaperone activity at a late step during L1 retrotransposition, extend the region of ORF1p that is known to be critical for its functional interactions with nucleic acids, and enhance understanding of nucleic acid chaperone activity

The Impact of CpG Island on Defining Transcriptional Activation of the Mouse L1 Retrotransposable Elements

BACKGROUND: L1 retrotransposable elements are potent insertional mutagens responsible for the generation of genomic variation and diversification of mammalian genomes, but reliable estimates of the numbers of actively transposing L1 elements are mostly nonexistent. While the human and mouse genomes contain comparable numbers of L1 elements, several phylogenetic and L1Xplore analyses in the mouse genome suggest that 1,500-3,000 active L1 elements currently exist and that they are still expanding in the genome. Conversely, the human genome contains only 150 active L1 elements. In addition, there is a discrepancy among the nature and number of mouse L1 elements in L1Xplore and the mouse genome browser at the UCSC and in the literature. To date, the reason why a high copy number of active L1 elements exist in the mouse genome but not in the human genome is unknown, as are the potential mechanisms that are responsible for transcriptional activation of mouse L1 elements. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the promoter sequences of the 1,501 potentially active mouse L1 elements retrieved from the GenBank and L1Xplore databases and evaluated their transcription factors binding sites and CpG content. To this end, we found that a substantial number of mouse L1 elements contain altered transcription factor YY1 binding sites on their promoter sequences that are required for transcriptional initiation, suggesting that only a half of L1 elements are capable of being transcriptionally active. Furthermore, we present experimental evidence that previously unreported CpG islands exist in the promoters of the most active T(F) family of mouse L1 elements. The presence of sequence variations and polymorphisms in CpG islands of L1 promoters that arise from transition mutations indicates that CpG methylation could play a significant role in determining the activity of L1 elements in the mouse genome. CONCLUSIONS: A comprehensive analysis of mouse L1 promoters suggests that the number of transcriptionally active elements is significantly lower than the total number of full-length copies from the three active mouse L1 families. Like human L1 elements, the CpG islands and potentially the transcription factor YY1 binding sites are likely to be required for transcriptional initiation of mouse L1 elements

The small satellite NINA-MITA to study galactic and solar cosmic rays in low-altitude polar orbit

Abstract The satellite MITA, carrying on board the scientific payload NINA-2, was launched on July the 15th, 2000 from the cosmodrome of Plesetsk (Russia) with a Cosmos-3M rocket. The satellite and the payload are currently operating within nominal parameters. NINA-2 is the first scientific payload for the technological flight of the Italian small satellite MITA. The detector used in this mission is identical to the one already flying on the Russian satellite Resurs-O1 n.4 in a 840-km sun-synchronous orbit, but makes use of the extensive computer and telemetry capabilities of MITA bus to improve the active data acquisition time. NINA physics objectives are to study cosmic nuclei from hydrogen to iron in the energy range between 10 MeV/n and 1 GeV/n during the years 2000–2003, that is the solar maximum period. The device is capable of charge identification up to iron with isotope sensitivity up to oxigen. The 87.3 degrees, 460 km altitude polar orbit allows investigations of cosmic rays of solar and galactic origin, so to study long and short term solar transient phenomena, and the study of the trapped radiation at higher geomagnetic cutoff

THE SPACE TELESCOPE NINA: RESULTS OF A BEAM TEST CALIBRATION

Abstract In June 1998 the telescope NINA will be launched in space on board of the Russian satellite Resource-01 n.4. The main scientific objective of the mission is the study of the anomalous, galactic and solar components of the cosmic rays in the energy interval 10–200 MeV/n. The core of the instrument is a silicon detector whose performances have been tested with a particle beam at the GSI Laboratory in Germany in 1997; we report here on the results obtained during the beam calibration

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Light Isotope Abundances in Solar Energetic Particles measured by the Space Instrument NINA

This article reports nine Solar Energetic Particle events detected by the instrument NINA between October 1998 and April 1999. NINA is a silicon-based particle detector mounted on-board the Russian satellite Resurs-01-N4, which has flown at an altitude of about 800 km in polar inclination since July 1998. For every solar event the power-law He4 spectrum across the energy interval 10--50 MeV/n was reconstructed, and spectral indexes, gamma, from 1.8 to 6.8 extracted. Data of He3 and He4 were used to determine the He3/He4 ratio, that for some SEP events indicated an enrichment in He3. For the 1998 November 7 event the ratio reached a maximum value of 0.33+- 0.06, with spectral indexes of gamma = 2.5 +- 0.6 and gamma = 3.7 +- 0.3 for He3 and He4, respectively. The He3/He4 ratio averaged over the remaining events was 0.011 +- 0.004. For all events the deuterium-to-proton ratio was determined. The average value over all events was (3.9+-1.4) 10^{-5} across the energy interval 9--12 MeV/n. For one event (1998 November 24) this ratio yielded approximately 10 times higher than normal coronal values. Upper limits on the H3/H1 counting ratio for all events were determined. For the 1998 November 14 SEP event the high flux of heavy particles detected made it possible to reconstruct the carbon and oxygen flux.Comment: 42 pages, 14 figures, submitted to Journal of Geophysical Researc

Burst of Young Retrogenes and Independent Retrogene Formation in Mammals

Retroposition and retrogenes gain increasing attention as recent studies show that they play an important role in human new gene formation. Here we examined the patterns of retrogene distribution in 8 mammalian genomes using 4 non-mammalian genomes as a contrast. There has been a burst of young retrogenes not only in primate lineages as suggested in a recent study, but also in other mammalian lineages. In mammals, most of the retrofamilies (the gene families that have retrogenes) are shared between species. In these shared retrofamilies, 14%–18% of functional retrogenes may have originated independently in multiple mammalian species. Notably, in the independently originated retrogenes, there is an enrichment of ribosome related gene function. In sharp contrast, none of these patterns hold in non-mammals. Our results suggest that the recruitment of the specific L1 retrotransposons in mammals might have been an important evolutionary event for the split of mammals and non-mammals and retroposition continues to be an important active process in shaping the dynamics of mammalian genomes, as compared to being rather inert in non-mammals