SignificanceCircular RNAs (circRNAs) play critical physiologic functions, but it is not known whether human DNA viruses express circRNAs. We surveyed Epstein−Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) tumors and cell lines, and found specific circRNAs expressed from both viruses. EBV circular BamHI A rightward transcripts (circBARTs) were expressed in all EBV tumor latency forms, including all EBV-infected posttransplant lymphoproliferative disease tumors tested, whereas EBV circBHLF1 and circLMP2 were more variably expressed. KSHV expressed circvIRF4 constitutively in primary effusion lymphoma cell lines, while the polyadenylated nuclear locus promiscuously generated variable, inducible, and bidirectional circRNAs. Tumor virus circRNAs can be long-lived, unique tumor biomarkers that may also open new research opportunities into understanding how these viruses cause cancer.

Summary MicroRNAs (miRNAs) are short RNA gene regulators typically produced from primary transcripts that are cleaved by the nuclear Microprocessor complex, with the resulting precursor miRNA hairpins exported by Exportin-5 and processed by cytoplasmic Dicer to yield two (5p- and 3p-) miRNAs. Here, we document Microprocessor-independent 7-methylguanosine (m7G) capped pre-miRNAs, whose 5′ ends coincide with transcription start sites, while the 3′ ends are most likely generated by transcription termination. By establishing a small RNA Cap-seq method that employs the cap-binding protein eIF4E, we identified a group of murine m7G-capped pre-miRNAs genome-wide. The m7G-capped pre-miRNAs are exported via the PHAX-Exportin-1 pathway. After Dicer cleavage, only the 3p-miRNA is efficiently loaded onto Argonaute to form a functional microRNP. This unusual miRNA biogenesis pathway, which differs in pre-miRNA synthesis, nuclear-cytoplasmic transport and guide strand selection, enables the development of shRNA expression constructs that produce a single 3p-siRNA.

Interest in the superconducting proximity effect has been reinvigorated recently by novel optoelectronic applications as well as by the possible emergence of the elusive majorana fermion at the interface between topological insulators and superconductors. Here we produce high-temperature superconductivity in Bi 2 se 3 and Bi 2 Te 3 via proximity to Bi 2 sr 2 CaCu 2 o 8 + δ , to access higher temperature and energy scales for this phenomenon. This was achieved by a new mechanical bonding technique that we developed, enabling the fabrication of highquality junctions between materials, unobtainable by conventional approaches. We observe proximity-induced superconductivity in Bi 2 se 3 and Bi 2 Te 3 persisting up to at least 80 K-a temperature an order of magnitude higher than any previous observations. moreover, the induced superconducting gap in our devices reaches values of 10 mV, significantly enhancing the relevant energy scales. our results open new directions for fundamental studies in condensed matter physics and enable a wide range of applications in spintronics and quantum computing.

During the regeneration of Drosophila imaginal discs, cellular identities can switch fate in a process known as transdetermination. For leg-to-wing transdetermination, the underlying mechanism involves morphogens such as Wingless that, when activated outside their normal context, induce ectopic expression of the wing-specific selector gene vestigial. Polycomb group (PcG) proteins maintain cellular fates by controlling the expression patterns of homeotic genes and other developmental regulators. Here we report that transdetermination events are coupled to PcG regulation. We show that the frequency of transdetermination is enhanced in PcG mutant flies. Downregulation of PcG function, as monitored by the reactivation of a silent PcG-regulated reporter gene, is observed in transdetermined cells. This downregulation is directly controlled by the Jun amino-terminal kinase (JNK) signalling pathway, which is activated in cells undergoing regeneration. Accordingly, transdetermination frequency is reduced in a JNK mutant background. This regulatory interaction also occurs in mammalian cells, indicating that the role of this signalling cascade in remodelling cellular fates may be conserved.