Our newest publication is out!
We showed that the yeast core factor (CF) binds and specifically recognizes promoter DNA in a two-step process, after which it will recruit RNA Polymerase I, inducing DNA bending and melting to start the transcription process.
https://academic.oup.com/nar/article/54/5/gkag153/8495788
#academicChatter #publication #science #nucleicAcidsResearch #nucleicAcids #yeast #dna #transcription
Mixtures of peptides and nucleic acids tend to demix and form coacervate droplets. Here, the authors show that even short peptides and oligonucleotides form droplets. DNA and RNA impart different properties to these protocells – stability, fluidity and the potential to host RNA chemistry.
How did primitive membranes form at the #OriginOfLife and how did they evolve into the cellular envelopes of modern cells?
Exciting talk by Claudia Bonfio about the non-enzymatic formation of phospholipids under conditions that are plausible for early Earth. https://pubs.rsc.org/en/content/articlelanding/2024/sc/d4sc05362a (1/2)
#Chemistry #OriginOfLife #lipid #membrane #evolution #LipidTime #NucleicAcids
Interesting bioRxiv preprint by the group of Matt Disney. They used fully functionalized fragments to enrich their targets and identify their binding sites on #RNA. Interesting insights into preferential binding to UTRs and the construction of RiboTACs.
https://www.biorxiv.org/content/10.1101/2025.11.05.686775v1
#NucleicAcids #TargetedDegradation #Chemistry #ChemBio
RNA folds are abundant in mammalian cells yet poorly characterized as small-molecule targets. We present a scalable, unbiased live-cell pipeline that maps where small molecules bind RNA across the human transcriptome and convert those binders into selective degraders. A 200-member fragment library bearing diazirine/alkyne handles yielded 23 RNA-binding candidates. Chem-CLIP-Map-Seq in MDA-MB-231 cells identified 723 RNA targets and their binding sites, revealing a strong bias toward 5'; and 3'; untranslated regions (UTRs) in mRNAs and enrichment at thermodynamically stable structures, with limited binding to non-coding RNAs. Expression level and local stability contributed to engagement. An integrated machine-learning model trained on multiple fingerprints distinguished binders from non-binders, and highlighted chemotypes and physicochemical features that favor RNA recognition. Four fragments were converted to a Ribonuclease Targeting Chimera (RiboTAC) to recruit Rnase L to degrade targeted mRNAs. Despite broad binding, cleavage was highly selective, with X1-RiboTAC degrading MPP7 and SSC4D mRNAs in an RNase L-dependent manner and reducing their protein levels. A competitive profiling workflow quantified in-cell target occupancy and guided optimization of the RNA-binding module to reprogram selectivity: an X1 derivative produced an MPP7-selective RiboTAC that lowered MPP7 mRNA levels and suppressed breast-cancer cell migration, while sparing SSC4D transcripts. This end-to-end framework, including transcriptome-wide mapping, data-driven rules, and tunable degradation, establishes practical principles for ligandable RNA sites in cells and enables rational design of RNA-targeted small molecules and degraders. ### Competing Interest Statement MDD Is a founder of Expansion and Ribonaut therapeutics. JLC-D is a founder of Ribonaut therapeutics. NIH Common Fund, CA249180A NIH Common Fund, GM133810 NIH Common Fund, https://ror.org/001d55x84, CA257090 Muscular Dystrophy Association, https://ror.org/01frxsf98, 963835
In the second episode of our new EXplained series, we highlight the #ClusterofExcellence NUCLEATE. At our #university, it is represented by Stefan Engelhardt, who shares insights into #nucleic-acid based #medicine: http://go.tum.de/139582
📷 ProLehre
In our "EXplained" video series, we present the seven Clusters of Excellence with which our university is entering the next funding phase of the Excellence Strategy. In the second episode, we get to know the new cluster NUCLEATE, which is represented at TUM by Prof. Stefan Engelhardt.
Read the interview with Stefan Engelhardt, our Professor of #Pharmacology and #Toxicology, who talks about the new #ClusterofExcellence, #NUCLEATE, which explores the function and regulation of #nucleicacids: http://go.tum.de/705241 🧬
📷A. Heddergott
Piia Bartos
StructBiolCommunications
Stephan Hacker
Stephan Hacker
Technische Universität München
ZPONZ