Activation of the Endonuclease that Defines mRNA 3' Ends Requires Incorporation into an 8-Subunit Core Cleavage and Polyadenylation Factor Complex.

Cleavage and polyadenylation factor (CPF/CPSF) is a multi-protein complex essential for formation of eukaryotic mRNA 3' ends. CPF cleaves pre-mRNAs at a specific site and adds a poly(A) tail. The cleavage reaction defines the 3' end of the mature mRNA, and thus the activity of the endonuclease is highly regulated. Here, we show that reconstitution of specific pre-mRNA cleavage with recombinant yeast proteins requires incorporation of the Ysh1 endonuclease into an eight-subunit "CPFcore" complex. Cleavage also requires the accessory cleavage factors IA and IB, which bind substrate pre-mRNAs and CPF, likely facilitating assembly of an active complex. Using X-ray crystallography, electron microscopy, and mass spectrometry, we determine the structure of Ysh1 bound to Mpe1 and the arrangement of subunits within CPFcore. Together, our data suggest that the active mRNA 3' end processing machinery is a dynamic assembly that is licensed to cleave only when all protein factors come together at the polyadenylation site.

RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination.

BACKGROUND: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. RESULTS: Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25's endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. CONCLUSIONS: Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity.

9,400 years of cosmic radiation and solar activity from ice cores and tree rings.

Understanding the temporal variation of cosmic radiation and solar activity during the Holocene is essential for studies of the solar-terrestrial relationship. Cosmic-ray produced radionuclides, such as (10)Be and (14)C which are stored in polar ice cores and tree rings, offer the unique opportunity to reconstruct the history of cosmic radiation and solar activity over many millennia. Although records from different archives basically agree, they also show some deviations during certain periods. So far most reconstructions were based on only one single radionuclide record, which makes detection and correction of these deviations impossible. Here we combine different (10)Be ice core records from Greenland and Antarctica with the global (14)C tree ring record using principal component analysis. This approach is only possible due to a new high-resolution (10)Be record from Dronning Maud Land obtained within the European Project for Ice Coring in Antarctica in Antarctica. The new cosmic radiation record enables us to derive total solar irradiance, which is then used as a proxy of solar activity to identify the solar imprint in an Asian climate record. Though generally the agreement between solar forcing and Asian climate is good, there are also periods without any coherence, pointing to other forcings like volcanoes and greenhouse gases and their corresponding feedbacks. The newly derived records have the potential to improve our understanding of the solar dynamics and to quantify the solar influence on climate.

The Cenozoic palaeoenvironment of the Arctic Ocean.

The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.

41Ca, 14C and 10Be concentrations in coral sand from the Bikini atoll.

Activation measurements of materials exposed to nuclear bomb explosions are widely used to reconstruct the neutron flux for retrospective dosimetry. In this study the applicability of coral CaCO3 as a biogenic neutron fluence dosimeter is tested. The long-lived radioisotopes (41)Ca, (14)C and (10)Be, which had been produced in nuclear bomb explosions, are measured in several coral sand samples from the Bikini atoll at the 600 kV and 200 kV AMS facilities of ETH Zurich. Elevated concentrations of all studied isotopes are found in a sample from the crater that was initially formed by the high-yield nuclear explosion Castle Bravo in 1954 and that had been used as site for several tests afterward. The observed (14)C concentration is considered too large to originate from neutron irradiation of CaCO3 alone. The relatively low concentration of (10)Be found in the crater sample indicates that production of (10)Be during nuclear bomb testing is generally minor. A simple neutron fluence reconstruction is performed on basis of the (41)Ca/(40)Ca ratio.

Near-synchronous interhemispheric termination of the last glacial maximum in mid-latitudes.

Isotopic records from polar ice cores imply globally asynchronous warming at the end of the last glaciation. However, 10Be exposure dates show that large-scale retreat of mid-latitude Last Glacial Maximum glaciers commenced at about the same time in both hemispheres. The timing of retreat is consistent with the onset of temperature and atmospheric CO2 increases in Antarctic ice cores. We suggest that a global trend of rising summer temperatures at the end of the Last Glacial Maximum was obscured in North Atlantic regions by hypercold winters associated with unusually extensive winter sea ice.

Low slip rates and long-term preservation of geomorphic features in Central Asia.

In order to understand the dynamics of the India Asia collision zone, it is important to know the strain distribution in Central Asia, whose determination relies on the slip rates for active faults. Many previous slip-rate estimates of faults in Central Asia were based on the assumption that offset landforms are younger than the Last Glacial Maximum (approximately 20 kyr ago). In contrast, here we present surface exposure ages of 40 to 170 kyr, obtained using cosmogenic nuclide dating, for a series of terraces near a thrust at the northern margin of the Tibetan Plateau. Combined with the tectonic offset, the ages imply a long-term slip rate of only about 0.35 mm x yr(-1) for the active thrust, an order of magnitude lower than rates obtained from the assumption that the terraces formed after the Last Glacial Maximum. Our data demonstrate that the preservation potential of geomorphic features in Central Asia is higher than commonly assumed.