25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Integrative structural biology of non-coding RNA-protein complexes: telomerase and 7SK

28 Aug 2019, 10:30
35m
Max Kade Auditorium (Henry Ford Building)

Max Kade Auditorium

Henry Ford Building

Invited talk Biological applications Biomolecules

Speaker

Prof. Juli Feigon (University of California Los Angeles)

Description

Telomerase and 7SK are essential eukaryotic RNA-protein complexes (RNPs) involved in telomeric DNA synthesis and regulation of mRNA transcription, respectively. Each comprises a non-coding RNA and constitutively and/or transiently associated proteins. Telomerase maintains the DNA at the ends of linear chromosomes, thereby preventing genomic instability. Its catalytic core is a non-coding telomerase RNA (TER) and a unique telomerase reverse transcriptase (TERT); other associated proteins are involved in biogenesis, assembly, recruitment to telomeres, and recruitment of other proteins of the DNA synthesis machinery. TERT uses a template complementary to ~1.5 telomere repeats in TER to repetitively synthesize the telomere repeat sequence at the 3’ end of the DNA (TTGGGG in ciliates, TTAGGG in vertebrates), but this template alone is insufficient for activity with TERT. Multiple steps of single-stranded telomeric DNA template binding/realignment, nucleotide addition, strand separation, and template translocation are required for synthesis of a single telomere repeat and telomere repeat addition processivity (RAP). We have been using an integrative structural biology approach combining NMR spectroscopy, X-ray crystallography, mass spectrometry, and electron microscopy to study the structure and function of telomerase from the ciliate Tetrahymena and from humans. I will discuss how our NMR studies of telomerase RNA structure and dynamics have been combined with cryo electron microscopy to help elucidate the roles of TER and proteins in this remarkable enzyme. I will also present recent NMR and X-ray crystallography results on the human long-noncoding RNA 7SK and two of its protein partners Larp7 and methylphosphate capping enzyme (MePCE).

Primary author

Prof. Juli Feigon (University of California Los Angeles)

Presentation Materials

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