Yale University School of Medicine & HHMI, New Haven
Saturday, 5 September, 17:45 - 18:30 Hall 1
Nuclear non-coding RNAs of viral and cellular origin: more surprises
EBER2 is a highly abundant nuclear non-coding RNA expressed by Epstein–Barr virus (EBV). Probing its possible chromatin localization by Capture Hybridization Analysis of RNA Targets (CHART) revealed EBER2’s presence at the terminal repeats (TRs) of the latent EBV genome, overlapping previously identified binding sites for the important B-cell transcription factor PAX5. EBER2 interacts with and is required for PAX5 localization to the TRs. Knockdown of EBER2 or PAX5 decreases EBV lytic replication, underscoring the essential role of the TRs in viral replication, which is known to be linked to the onset of EBV-associated tumours. Recruitment of the EBER2-PAX5 complex is mediated by base pairing between EBER2 and nascent transcripts from the TR locus. The interaction is evolutionarily conserved in the related primate herpes virus CeHV15 despite great sequence divergence in both EBER2 and the TRs. Using base pairing with nascent transcripts to guide an interacting transcription factor to its DNA target site in chromatin is a previously undescribed function for a trans-acting non-coding RNA. We have uncovered a novel transcript type derived from human protein-coding genes that is represented by thousands of examples genome-wide. These RNAs, which we call DoGs for downstream of gene containing transcripts, are inducible by osmotic stress through an IP3 receptor signalling-dependent pathway, indicating active regulation. DoGs possess long non-coding regions (often >45 kb) and remain chromatin bound. Their levels are increased by decreased termination of the upstream transcript, a previously undescribed mechanism for rapid transcript induction. Relative depletion of polyA signals in DoG regions correlates with increased levels of DoGs after osmotic stress. DoGs may play a role in reinforcing the nuclear scaffold after stress.
Joan A. Steitz earned her BS in Chemistry from Antioch College (1963) and her PhD from Harvard (1967), with Jim Watson. During postdoctoral study at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, with Francis Crick and Sydney Brenner, she identified ribosome binding sites on the R17 phage RNA. She has been at Yale since 1970. In 1979, her student Michael Lerner discovered that small nuclear (sn)RNAs bind proteins targeted by patient autoantibodies, leading to the identification of snRNPs and their essential roles in pre-mRNA splicing. Their studies of non-coding (nc)RNAs continued with the discovery of small nucleolar (sno)RNAs of the Box C/D class, small Cajal body RNAs (scaRNAs) and the snRNPs of the minor (U12-dependent) spliceosome. Recently, they have studied the biogenesis and function of microRNAs, as well as uncovering functions for the roles of abundant ncRNAs made gamma herpesviruses, including EBV and KSHV.
PETER WALTER US
University of California, San Francisco
Monday, 7 September, 09:00 - 09:45 Hall 1
The Serendipitous Path of Discovery: from Protein Folding to Cognition
A screen for small molecule modulators of the unfolded protein response yielded ISRIB, a drug-like compound that with high efficacy renders cells insensitive to translational inhibition by phosphorylation of eIF2. ISRIB proved to be a cognitive enhancer in rodents, significantly improving long-term memory of wild-type animals in behavioural assays.
Peter Walter is currently a Distinguished Professor of Biochemistry and Biophysics at UCSF and a HHMI Investigator. He graduated from the Free University of Berlin in 1976, and received his Masters of Science in Organic Chemistry from Vanderbilt University in 1977. In 1981 he obtained his PhD in Biochemistry at The Rockefeller University. In 1983, Peter joined the faculty of the Department of Biochemistry and Biophysics at the University of California at San Francisco, and served as Department Chair from 2001 until 2008. He is the current President-Elect of the American Society of Cell Biology. Peter’s awards include the Eli Lilly Award, the Passano Award, the Wiley Prize, the Stein & Moore Award, the Gairdner Award, the E.B. Wilson Medal, the Otto Warburg Medal, the Jung Prize, the 2012 Ehrlich and Darmstaedter Prize, the 2014 Shaw Prize, the 2014 Lasker Award and the 2015 Vilcek Prize.