I am no longer actively using this account. Please find me on the other place. 🦋

Come join the amazing members of my team 🤩🤩!

We have an open #postdoc position to study the molecular mechanisms of #DNArepair !🧬🔬 The project will build on recent findings https://t.co/TDxCrkgZKb and established collaborations, using #cryoEM and #SingleMolecule imaging. Access to fantastic facilities @MRC_LMB .

CryoEM community: we encourage you to submit applications to the Almeida Award #cryoEM BPS subgroup:

Unfortunately I had to leave the conference very suddenly and unexpectedly due to a family emergency. I really missed meeting and speaking with so many people. Many apologies - I would be happy to zoom meet with anyone who wants to chat - please drop me an email!

I presented this work at #EESRNA @embl @EMBLHeidelberg An amazing meeting organised by @LabConti @OlivierDuss @torbenheick and Karla Neugebauer!!

Preprint here:

The enzymatic machineries of gene expression (deadenylation complexes, RNA polymerases) are highly conserved. .... but the evolutionary plasticity of IDRs found in a multitude of regulators (RNA adaptors, transcription factors) allows rewiring of gene expression programs. 10/

This interaction mechanism has parallels with other processes in gene expression including transcription and decapping. Continuous tuning likely occurs within multiple steps of gene expression ... 9/

We conclude that phosphorylation can result in a rheostat-like response on the multivalent interaction allowing ‘tuning’ of deadenylation activity. This is a common principle across multiple RNA adaptors (e.g. Pumilio proteins, TTP/ZFP36) in yeast and human complexes. 8/

Excitingly, this multivalency can be regulated by multi-site phosphorylation of the IDR. This modulates IDR charge and dynamics to ‘tune’ deadenylation rate. 7/

Targeted mutations in individual residues across the IDR (or in dispersed surface pockets of Ccr4-Not) results in a *graded* decrease in deadenylation activity, pointing towards a multivalent interaction. 6/

In this work, James used NMR with @connyyu , crosslinking mass spec with @RappsilberLab and biochemical reconstitution to discover that dispersed regions within the IDRs interact with multiple conserved binding sites on Ccr4-Not. 5/

Intrinsically-disordered regions (IDRs) in RNA adaptors interact with Ccr4-Not. This promotes deadenylation of bound transcripts. 4/

But how are specific mRNAs targeted for decay at the correct time? Many different ‘RNA adaptor’ proteins (RNA-binding proteins) tether specific transcripts directly to Ccr4-Not. 3/

Poly(A) tails control translation and stability of eukaryotic mRNAs. The Ccr4-Not deadenylation complex shortens these tails to control gene expression in a regulated and context-dependent manner. 2/

New work from the lab! James Stowell led this project showing the importance of multivalency and phospho-regulation in mRNA decay. This has many parallels with other mechanisms in gene expression... 🧵 1/ #RNA #NMR #bioRxiv @MRC_LMB @ERC_Research

Great fun with the @RappsilberLab ! Photo-crosslinking improves the contrast of crosslinking mass spectrometry.

Very cool structure!

I am really looking foward to working with @SjorsScheres as Joint Head of Structural Studies @MRC_LMB !