Markus Hafner

Oxidative stress sensing by the translation elongation machinery promotes production of detoxifying selenoproteins Selenocysteine, incorporated into polypeptides at recoded termination codons, plays an essential role in redox biology. Using GPX1 and GPX4, selenoenzymes that mitigate oxidative stress, as reporters,...

Colliding ribosomes are potent signals of cellular stress. But do cells use ‘programmed’ ribosome collisions to regulate gene expression? I’m excited to present a new story from my lab led by Frederick Rehfeld(@fred-rehfeld.bsky.social) which revealed that the answer is YES! Read on to find out how👇

👀

Thanks!

Such a form of “multifactor auyhorization” of course protects posttranscriptional regulatory pathways from aberrant expression of individual components - as we observed in the case of DND1/NANOS3: their ectopic expression sends any cell into cell-cycle arrest.

The specific motif built up by these two RBPs cannot be identified by studying each of them in isolation, so one important question we would like to raise is: How many RBPs form heteromultimeric complexes with specificity other than the sum of the individual RBPs?

This work was spearheaded by Masataka Suzawa in my (NIAMS) and Chen Qiu in Traci Hall’s lab (NIEHS IRP) and initiated together with Masashi Yamaji’s group at Cincinnati Children’s. Wonderful collaboration with @eugenevalkov.bsky.social and Vittorio Sartorelli.

The DND1-NANOS3 complex shapes the primordial germ cell transcriptome via a heptanucleotide sequence in mRNA 3'UTRs The RNA-binding proteins DND1 and NANOS3 are essential for primordial germ cell survival. Their co-immunoprecipitation and overlapping loss-of-function phenotypes suggest joint function, yet how they ...

www.biorxiv.org/content/10.1...

Delighted to share the story of two germline RBPs - one with little (DND1) and one with no (NANOS3) intrinsic sequence-specificity - that together build a continuous RNA binding surface recognizing a 7-mer (AUGAAUU) in target mRNA 3’UTRs, leading to deadenylation.

Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation Development of LOV-domain-controlled ligase for translation localization (LOCL-TL), an optogenetic approach for monitoring translation with codon resolution at any defined subcellular location under p...

#RNAbiology #RNAlocalization #LocalizedTransaltion
www.cell.com/cell/fulltex...

Predicting the translation efficiency of messenger RNA in mammalian cells Nature Biotechnology - A deep convolutional neural network model predicts the influence of the full-length mRNA sequence on translation efficiency.

Very excited that our most significant work, a collaboration w/ Dr. Can Cenik at UT Austin on translational gene regulation, was finally published in Nature Biotechnology in a dual set of studies:

Paper 1 -- an AI model trained to predict translation rates from mRNA sequences: rdcu.be/exN1l

SPIDR enables multiplexed mapping of RNA-protein interactions and uncovers a mechanism for selective translational suppression upon cell stress SPIDR, a massively multiplexed method that simultaneously maps dozens of RNA-binding proteins to their RNA targets at single-nucleotide resolution, uncovers new RNA-protein interactions and provides c...

www.cell.com/cell/fulltex...

Intracellular pathogen effector reprograms host gene expression by inhibiting mRNA decay - Nature Communications Intracellular pathogens hijack host gene expression to subvert cellular processes. Here, the authors show that Legionella pneumophila’s PieF effector inhibits the human CCR4-NOT deadenylation machiner...

Happy to share the latest work on a bacterial protein that inhibits human mRNA decay machinery, in collaboration with @smlea.bsky.social #RNAsky

www.nature.com/articles/s41... Intracellular pathogen effector reprograms host gene expression by inhibiting mRNA decay | Nature Communications

Predicting expression-altering promoter mutations with deep learning Only a minority of patients with rare genetic diseases are currently diagnosed by exome sequencing, suggesting that additional unrecognized pathogenic variants may reside in non-coding sequence. Here,...

Predicting expression-altering promoter mutations with deep learning www.science.org/doi/10.1126/... - well this looks useful!

Trinucleotide substrates under pH–freeze–thaw cycles enable open-ended exponential RNA replication by a polymerase ribozyme Nature Chemistry - Models of abiotic RNA replication suffer from inherent product inhibition arising from the high stability of RNA duplexes. Now, it has been shown that RNA trinucleotide...

New paper from my group rdcu.be/eoaRr "Trinucleotide substrates under pH–freeze–thaw cycles enable open-ended exponential RNA replication by a polymerase ribozyme" in Nature Chemistry — great collaboration with attwaterlab.uk.

Excited to finally be heading to RNA 2025 in San Diego! Have worked with amazing colleagues to co-organize this meeting so I can’t wait to see all the exciting science and connect with colleagues! @rnabiologist.bsky.social @kkarbstein.bsky.social

m6A alters ribosome dynamics to initiate mRNA degradation m6A is a potent inducer of ribosome stalling and collisions that trigger YTHDF-mediated mRNA degradation, a process that highlights the ribosome as a critical sensor linking translation dynamics to m6...

Very interesting work from Samie Jaffrey's lab: m6A promotes ribosome collisions, with big effects on RNA stability. #RNASky

www.cell.com/cell/fulltex...

The whole-genome sequences of herding dogs reveal how selection has sculpted the unique behavioral traits
www.science.org/doi/10.1126/...

Congratulations to MSK’s Dr. Stefanie Gerstberger for receiving the @theaacr.bsky.social Women in Cancer Research Scholar Award! 🎉 #AACR25

Learn more about her fascinating work investigating #phenotypic plasticity & chemo resistance in colorectal cancer here: www.abstractsonline.com/pp8/#!/20273...

Complete sequencing of ape genomes - Nature Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evol...

Our primate T2T paper came out in Nature yesterday! It was a huge effort and I'm so grateful that I got the opportunity to work with this amazing group of scientists over the first two years of my PhD!
www.nature.com/articles/s41...

Rbm24a dictates mRNA recruitment for germ granule assembly in zebrafish
Yizhuang Zhang et al show that loss of maternal Rbm24a causes complete degradation of germ granules and disappearance of primordial germ cells
www.embopress.org/doi/full/10....

#RNAsky #RNAbiology

The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells - Nature Immunology Panzer and colleagues show that the integrated stress response pathway regulates cytokine translation in CD4+ TRM cells during homeostasis and inflammation.

Asada et al 2025
"The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells"
@natureportfolio.nature.com
www.nature.com/articles/s41...

The regulation and function of post-transcriptional RNA splicing Nature Reviews Genetics, Published online: 11 April 2025; doi:10.1038/s41576-025-00836-zPost-transcriptional splicing has emerged as a key layer of gene expression regulation but is challenging to differentiate from co-transcriptional splicing. The authors review methodologies to detect post-transcriptional splicing, the mechanisms controlling splicing timing and how the temporal regulation of splicing affects gene expression.

ICYMI: New online! The regulation and function of post-transcriptional RNA splicing

Structural basis for nucleolin recognition of MYC promoter G-quadruplex The MYC oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than...

🧬@science.org Structural basis for nucleolin recognition of MYC promoter G-quadruplex | Science www.science.org/doi/10.1126/...
@cancer-inst-purdue.bsky.social danzhou-yang.com #DNA #StructuralBiology

I am happy to share the latest paper from the lab. We detail a tripartite cell-free translation system based on the separation of mRNAs, ribosomes and ribosome-depleted cytoplasmic lysate from human cells, allowing for flexible reconstitution of translation reaction.
#RNA #Ribosome

Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines - Nature Upon intramuscular administration, COVID-19 mRNA vaccines are primarily taken up by macrophages, in which the cellular machinery extends their poly(A) tails, thereby increasing mRNA stability and tran...

#RNA #RNASky

Highly sensitive method captures rare RNAs in blood to search for disease www.nature.com/articles/d41...
@nature.com
www.nature.com/articles/s41...

Integrator loss leads to dsRNA formation that triggers the integrated stress response Integrator (INT) prevents the escape of immature RNAPII to ensure full-length mRNA production. INT deficiency causes defects in RNAPII maturation that lead to premature termination, accumulation of immunogenic dsRNA, and activation of the integrated stress response (ISR) observed in patient cells.

Now online! Integrator loss leads to dsRNA formation that triggers the integrated stress response

A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance Soles et al. demonstrate that the combination of a 5′ splice site and a poly(A) junction constitutes a nuclear RNA degradation code that targets RNAs for degradation by the PAXT adaptor and the RNA ex...

A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance: Molecular Cell www.cell.com/molecular-ce...

#RNAsky #RNAbiology #RNAdecay

This is Ripley. He was nervous about taking the stairs. May have panicked a bit. 12/10

Exogenous RNA surveillance by proton-sensing TRIM25 Exogenous messenger RNAs (mRNAs) require cellular machinery for delivery and translation but also encounter inhibitory factors. To investigate their regulation, we performed genome-wide CRISPR screens...

www.science.org/doi/10.1126/...