Ana Tufegdzic Vidakovic

Wow, big congratulations Kelly! So well deserved! ☺️

We are excited to be recruiting a new tenure track group leader in the Structural Studies Division at MRC LMB! It is an amazing place to start your own lab.
@mrclmb.bsky.social

Please get in touch if you have any questions.
www.nature.com/naturecareer...

How did life arise from simple chemical building blocks?

New #LMBResearch led by @edogia.bsky.social in @philholliger.bsky.social group has identified a small self-replicating ribozyme that could be the answer.

Read more: mrclmb.ac.uk/news-events/...

Congratulations Kelly! 👏

It was great fun collaborating with Scott Berry's lab, as always! @scottbscience.bsky.social @cftbla.bsky.social
Wonderful to see this work online 🧪 🔬 🧫! How cells respond to changes in RNA Pol II abundance 👇

We have an opening for a research support officer. Come and join us! Please share.

Pre-pore and cis pores formed by full length perforin-2 during antigen escape from early phagosomes

Time for a new pre-print! How do dendritic cells control pore formation in their own endocytic compartments?

Our work shows that the unique transmembrane anchor of perforin-2 does not protect DC membranes, but instead it enables antigen escape during cross-presentation

doi.org/10.64898/202...

SET1/MLL complexes control transcription independently of H3K4me3 Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...

An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost!

www.biorxiv.org/content/10.6...

This was fantastic work led by @ivavitz.bsky.social , Yu Bao, Tea Toteva and Alastair Crisp. Also a wonderful collaboration with Mike Boemo's lab. 🧪🧬🧫

If the obstacles are not fixed by the time these Ser7-hyper-phosphorylated polymerases reach them, Ser7p protects these Pol II molecules from ubiquitylation and degradation to salvage a minimal pool of Pol II needed for recovery, preventing irreversible transcription shutdown.

Overall, we propose that stalling of elongating Pol II in gene bodies triggers Ser7p in trans, on polymerases just entering elongation, to "warn" them there are obstacles lying ahead.

We identify GSK3 as a Ser7 kinase, which is interesting in light of previous work by Kornblihtt and Marteijn labs implicating GSK3 in regulation of stalled Pol II.

Ser7p is a universal hallmark of stalled transcription: fundamentally different obstacles to elongating Pol II all cause induction of Ser7p. We find this is likely because they all cause Pol II backtracking - and Pol II backtracking alone is sufficient to induce profound Ser7p upregulation.

Mechanistically, Ser7p inhibits excessive degradation of Pol II by the Last resort pathway, and protects a minimal reserve of Pol II molecules needed for transcription recovery.

Pol II stalling is known to trigger two pathways: transcription-coupled NER (TC-NER) and the last resort ubiquitylation-degradation of Pol II. We find Ser7p represents a third pathway altogether. All three pathways are needed for transcription recovery after DNA damage.

Ser7p remains the least understood Pol II phospho-mark, with unknown function on protein coding genes. We find Ser7p is required for productive Pol II elongation and for transcription recovery after DNA damage.

We discovered that stalling of elongating Pol II in gene bodies triggers hyper-phosphorylation of Ser7 at the Pol II CTD. To our surprise, this didn't happen directly on stalled Pol II molecules but at a remote part of the gene - near the gene beginning, in the early elongation zone!

Stalling of elongating Pol II triggers Ser7 phosphorylation in trans to drive transcription recovery DNA is scattered with obstacles that stall RNA polymerase II (Pol II) and block the production of full-length transcripts. Two mechanisms are known to resolve stalled Pol II: transcription-coupled nuc...

Happy to share a new preprint from our lab, uncovering "spooky action at a distance" - for RNA Polymerase II:
www.biorxiv.org/content/10.6...

It is a privilege to join the international EMBO community and I look forward to meeting and exchanging ideas with fellow EMBO investigators! I am most grateful to my fantastic lab members who made this possible. 🧪🧫 🧬

Our dxChIP-seq protocol is now online! If you have a difficult chromatin target, you may want to give it a try (it also works for "easy" targets such as Pol II and histones).
www.sciencedirect.com/science/arti...

@mrclmb.bsky.social MRC LMB is looking for a new group leader in Chemical/Synthetic Biology. Come and join us in this fantastic institute! Core funding, amazing science all around you and great collaborative colleagues are just some of the highlights. Please share the news!

Looking forward to presenting at the Cambridge RNA club again! If you are interested in gene regulation and around Cambridge, stop by!

RNA meets protein decay Establishing the composition of RNAs and proteins that defines the identities and functions of cells relies not only on the regulated biosynthesis of these molecules, but also equally importantly, on…

~1 week left to register for the EMBO workshop on RNA meets protein decay! #EMBOrnaDecay
Come join us for a fun time and invigorating scientific discussions in Vienna!

meetings.embo.org/event/25-rna...

The first PhD student of our lab, 5'-Ivan Shlamovitz, has passed his viva with flying colours! What a special moment! The whole lab (and many friends at the LMB) are proud! 👏😁

Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss of INTS6 in h…

This was a fantastic team work led by Roberta Cacioppo, Alexander Gillis, Ivan Shlamovitz and Andrew Zeller. Also take a look at a complementary work by Svejstrup Lab: www.sciencedirect.com/science/arti...

We conclude that ARMC5 and Integrator phosphatase work in parallel to monitor the quantity and quality of Pol II complexes before they are licenced to enter elongation.

We conduct a synthetic lethality mini-screen and identify Integrator phosphatese compensates for the loss of ARMC5! When both Integrator phosphatase and ARMC5 are missing, excessive Pol II enters early elongation, but many of these are transcription-incompetent and fail to reach gene ends.

Loss of ARMC5 causes profound accumulation of Pol II both off-DNA and at gene beginnings, but not in gene bodies. Something else is preventing all this excess Pol II at initial stages of transcription to proceed into elongation. What is it?

But why would cells ubiquitylate and destroy promoter-proximal Pol II? We find that ARMC5 targets "defective" Pol II complexes! So what happens to transcription if this pathway is lost?

We find this new Ub Pol II form specifically comes from the promoter-proximal zone, leads to Pol II degradation, and identify the E3 ligase responsible is ARMC5-CUL3!