Nogales Lab

A unique honor to become a Foreign Member of the @royalsociety.org, together with my @ucberkeleyofficial.bsky.social colleague Stuart Russell and old friends like John Briggs, Asia Akhtar, Patrick Cramer or Ruth Lehmann. Learning about great science and science history was a real treat.

Very grateful to the Menéndez Pelayo International University for awarding me an honorary doctorate last Tuesday, July 8th, in the incomparable setting of the Magdalena Palace (Santander). On Monday I enjoyed a conversation with those interested in my career and science.

Structural insights into transcriptional regulation by the helicase RECQL5 - Nature Structural & Molecular Biology Florez Ariza and Lue et al. use cryo-electron microscopy to investigate how the RECQL5 helicase regulates transcription. Their structural findings suggest that RECQL5 can modulate RNA polymerase II’s ...

Our work, co-led by @alfredo0712.bsky.social and @nlue8.bsky.social is out in @natsmb.nature.com Shout out to coauthors P.Grob, B. Kaeser, J.Fang, and S. Kassube for their contributions and thanks to the reviewers for the suggestions that led to the final work.
www.nature.com/articles/s41...

BioPhySAL - First Salamanca International Advanced Biophysics and Structural Biology Course First Summer International Advanced Biophysics and Structural Biology Course. Eva Nogales - Carlos Bustamante.

So proud of the smashing success of the International Course in Biophysics co-organized with my @berkeleymcb.bsky.social colleague Carlos Bustamante and University of Salamanca @usaloficial.bsky.social
biophysal.org
Course ends with a Keynote from Nobel Laureate Richard Henderson🥇

Yesterday I had the pleasure to visit the Institute for Material Science in Madrid @icmm-csic.bsky.social. Thank you to Dr. Pedro Serana for his invitation to talk about cryo-EM and our latest microtubule studies 🧩🔬🧬

I spent a wonderful day in the Universidad de Córdoba at an interactive breakfast with faculty and students and giving a science presentation. Lovely to meet its Chancellor, Manuel Torralbo, and my friend and past collaborator Prof. Tina Domínguez-Martín.

It was an absolute pleasure to visit the IBiS, to meet its scientists, interact with its students, and visit beautiful Sevilla 🥰

Excited to have participated in the Third Symposium of Physical Chemistry in the Universidad Autónoma de Madrid @uam.es last week and honored that the Prizes for best student talk and best posters carried my name 🥰☺️

Que día tan emocionante volver a mi colegio en Colmenar Viejo y recibir el calor de sus profesores y sus alumnos. Gracias por darle mi nombre a vuestra biblioteca! 🥰

Deeply touched and honored by the Universidad Autónoma de Madrid, my alma mater, (@uam.es) making me Doctor Honoris Causa. Thank you to the Department of Physical Chemistry for nominating me for this recognition. It was a memorable day for me and my family👩‍🎓

Like a dream, my name next to that of @isabelallende.com, and to be recognized by Universidad Internacional Menéndez Pelayo UIMP. Soon after, Irene Vallejo @irenevalmore.bsky.social will receive the same honor. I feel proud to be linked to these truly inspiring, talented women! Thank you UIMP!

This week our lab had a double celebration: 1) Eva’s election into the @royalsociety.org and 2) Zhenlin’s new job in Southern University of Science and Technology, China. He will be missed but we wish him success and joy in his independent career!

Structural and biochemical studies of mobile retrotransposon proteins in action Autonomous non-long-terminal repeat (non-LTR) retrotransposons, including long interspersed elements (LINEs), are mobile genetic elements abundant in …

Check out our review article on the structural and functional studies of retrotransposon proteins by @akankshathawani.bsky.social together with Kathy Collins' lab.

www.sciencedirect.com/science/arti...

A huge shoutout to our former grad student Susanne Kassube (now PI) for leading our lab’s original study back in 2013 and setting the stage for this work. If you’re interested, check out our preprint for more details and stay tuned for the full paper! 7/7

Beyond a role in slowing down Pol II elongation, RECQL5 is known to decrease transcription stress. We propose that RECQL5 may help restart transcription from stalled Pol II by allosterically modulating Pol II’s translocation state. 6/7

Nucleotide binding (AMPPNP or ADP) causes the RECQL5 helicase domain to undergo a conformational change, pulling on the DNA to induce Pol II to shift to a post-translocation state. Meanwhile, the IRI module seems to serve as a stable anchor for RECQL5 binding. 5/7

The high resolution of our structures also enabled us to ask how RECQL5 affects Pol II, in particular its translocation state on a DNA/RNA scaffold. We found that Pol II occupies different translocation states when RECQL5 helicase is in its apo vs. nucleotide-bound form. 4/7

We report high-resolution structures of Pol II elongation complexes with RECQL5, visualizing interactions between RECQL5, Pol II, and DNA, confirming its role as a transcriptional roadblock. This required extensive data processing, as RECQL5 is very flexible! 3/7

RecQ helicases help safeguard genome stability. In this family, RECQL5 stands out as the only one to interact with and inhibit RNA Pol II, and it’s been shown to help decrease transcription stress. We used cryo-EM to investigate the molecular basis for this mechanism. 2/7

Structural insights into transcriptional regulation by the helicase RECQL5 Transcription and its regulation pose a major challenge for genome stability. The helicase RECQL5 has been proposed as an important factor to help safeguard the genome, and is the only member of the h...

Check out our lab’s latest work on the regulation of transcription by RECQL5 helicase! This work was co-led by @alfredo0712.bsky.social and @nlue8.bsky.social, with contributions from Patricia Grob, Ben Kaeser, Jie Fang, and Susanne Kassube. 1/7
www.biorxiv.org/content/10.1...

Cryo-EM: The Next 50 Years Symposium - YouTube January 11, 2025 - UC Berkeley

The recording of the talks is now available at youtube.com/playlist?lis...

I encourage you to apply and join us at @ucberkeleyofficial.bsky.social !

Our microtubule team at lunch with @ruizhangmt.bsky.social, who gave a spectacular seminar at UC Berkeley on his work on axonemes

The Cryo-EM: the next 50 years Symposium held yesterday at @ucberkeleyofficial.bsky.social was a smashing success!!

These two distinct inhibition mechanisms are determined by the unique location of H3K4me3 and H3K36me3 along the histone H3 tail and target two essential requirements for efficient trimethylation of histone H3K27 to exclude PRC2 activity from actively transcribe genes

The H3K4me3 modification binds to the well-characterized allosteric site in EED and can compete with allosteric activators of PRC2, however it lacks interactions with the EZH2 stimulatory response motif (SRM) and does not trigger allosteric activation like known PRC2 activators.

The tail-disengaged state reveals a novel binding geometry between PRC2 and the nucleosome that is incompatible with catalytic activity

We identified two states in cryo-EM analysis of PRC2 bound to H3K36me3 nucleosomes: 1) tail-engaged state that shows accommodation of modified H3 tails in the active site and 2) a tail-disengaged state that indicates H3K36me3 tails engage less efficiently with the PRC2 active site

H3K4me3 and H3K36me3 localize to sites of active transcription where H3K27me3 is absent and directly inhibit PRC2 activity in biochemical assays through unknown mechanisms. We determined cryo-EM structures of PRC2 bound to H3K4me3 and H3K36me3 modified nucleosome substrates.

Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications - Nature Structural & Molecular Biology Structures reveal that histone H3K36me3 and H3K4me3 modifications reduce Polycomb repressive complex 2 (PRC2) function through the inhibition of histone tail engagement and antagonistic binding to the...

Work led by graduate student @trinitycookis.bsky.social and coauthors Alexandria Lydecker, @paulsauer.bsky.social, and @kasinath-lab.bsky.social is out today where we looked at the inhibition of PRC2 by histone PTMs associated with regions of active transcription.

www.nature.com/articles/s41...