No abstract

LINE-1s are active human DNA parasites that are agents of genome dynamics in evolution and disease. These streamlined elements require host factors to complete their lifecycles, whereas hosts have developed mechanisms to combat retrotransposition’s mutagenic effects. As such, endogenous L1 expression levels are extremely low, creating a roadblock for detailed interactomic analyses. Here we describe a system to express and purify highly active L1 RNP complexes from human suspension cell culture and characterize the co-purified proteome, identifying 37 high-confidence candidate interactors. These datasets include known interactors PABPC1 and MOV10 and, with in-cell imaging studies, suggest existence of at least three types of compositionally and functionally distinct L1 RNPs. Among the novel findings, UPF1, a key nonsense-mediated decay factor, and PCNA, the polymerase-delta-associated sliding DNA clamp, were identified and validated. PCNA interacts with ORF2p via a PIP box motif; mechanistic studies suggest this occurs during or immediately after target-primed reverse transcription.

In the past few years wide-field optical and UV transient surveys as well as X-ray telescopes have allowed us to identify a few dozen candidate tidal disruption events (TDEs). While in theory the physical processes in TDEs are expected to be ubiquitous, a few distinct classes of TDEs have been observed. Some TDEs radiate mainly in NUV/optical while others produce prominent X-rays. Moreover, relativistic jets have been observed in only a handful of TDEs. This diversity might be related to the details of the super-Eddington accretion and emission physics relevant to TDE disks. In this Letter, we utilize novel three-dimensional general relativistic radiation magnetohydrodynamics simulations to study the super-Eddington compact disk phase expected in TDEs. Consistent with previous studies, geometrically thick disks, wide-angle optically-thick fast outflows and relativistic jets are produced. The outflow density and velocity depend sensitively on the inclination angle, and hence so does the reprocessing of emission produced from the inner disk. We then use Monte-Carlo radiative transfer to calculate the reprocessed spectra and find that that the observed ratio of optical to X-ray fluxes increases with increasing inclination angle. This naturally leads to a unified model for different classes of TDEs in which the spectral properties of the TDE depend mainly on the viewing-angle of the observer with respect to the orientation of the disk.