Isha Walawalkar, MPH

Composite SMG5-SMG6 PIN domain formation is essential for NMD - Nature Communications Execution of mRNA cleavage in nonsense-mediated decay remained elusive. The authors show that SMG5 complements SMG6 to form a highly active, composite endonuclease with expanded catalytic center that ...

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

Renowned Developmental Biologist Wins March of Dimes Prize March of Dimes names Dr. Leonard Zon winner of the 2026 Richard B. Johnston Jr., MD Prize for breakthroughs in developmental biology and treatments for blood disorders.

Big congrats to Dr. Len Zon for being awarded the 2026 @marchofdimes.org Richard B Johnston Jr, MD Prize for his work in #devbio. His pioneering research has illuminated how blood develops in embryos, leading to a deeper understanding of genetic blood diseases. www.marchofdimes.org/about/news/r... 🧪

Keeping cells fit Fragments of aberrant cytoplasmic mRNA pair with nuclear RNAs to augment transcription

@science.org Keeping cells fit | Science www.science.org/doi/10.1126/...

A genetically encoded device for transcriptome storage in mammalian cells Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and s...

Amazing: TimeVaults!

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

A small polymerase ribozyme that can synthesize itself and its complementary strand The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller?

Excited to share our latest work in @science.org on a new small polymerase.
1/n

Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmica...

@science.org Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation | Science www.science.org/doi/10.1126/...

Decoding RNA–protein interactions using high-throughput methods RNA-binding proteins (RBPs) constitute a diverse class of proteins essential for every stage of the gene expression process. Many RBPs are also linked to human diseases and pathologies. Understandi...

Happy to share the first review article from our lab!

We discuss the landscape of available high-throughput approaches for profiling RNA–protein interactions in vitro and in vivo.

We hope it will be useful when designing your next experiment.

www.tandfonline.com/doi/full/10....

#RNAsky

RBPscan: A quantitative in vivo tool for profiling RNA-binding protein interactions Kretov et al. introduce RBPscan, an RNA-editing-based platform that measures how RNA-binding proteins engage their targets in living cells. This approach quantifies the binding strength of protein-RNA...

I am thrilled to share our paper introducing RBPscan, a novel approach to profile RNA–protein interactions in living cells. Free access link at the end ⬇️ 🧵 1/
www.cell.com/molecular-ce...

We’re excited to share our latest preprint on the mechanism of excised linear intron stabilization in yeast! This work was led by PhD student @glennli.bsky.social and was a wonderful collaboration with @maxewilkinson.bsky.social. Link: www.biorxiv.org/content/10.6... (1/4)

Coordinating mRNA maturation: The U1 relay model Yoon et al. provide a broad overview of how all the RNA processing steps are intimately linked to transcription and to one another. They propose a U1 relay model as a general framework for understanding the mechanism for coupling transcription and RNA processing.

Online Now: Coordinating mRNA maturation: The U1 relay model Online now:

DNA-protein cross-links promote cGAS-STING–driven premature aging and embryonic lethality DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease...

Unrepaired DNA-protein crosslinks cause a process that leads to premature aging and embryonic lethality in mice.

The findings in Science reveal a previously unrecognized link between defective DNA repair and immune-driven inflammatory disease. https://scim.ag/4qdZWf9

What can stem cells tell us about autism and other developmental brain disorders?

Developed by JAX Professor Martin Pera, a new stem cell–based platform developed at JAX uses induced pluripotent stem cells (iPSCs) from eight genetically distinct strains of mice to unlock one of the biggest mysteries in genetics. Why does the same genetic mutation have little to no effect in one person while have potentially causing a devastating disease in another?

Image (top) - Brain cells created from induced pluripotent stem cells shown under a microscope in The Pera Lab at JAX. Text below reads: This new platform allows scientists to grow brain cells reliably from each strain, a major technical advance that opens the door to studying many other disease-linked genes in a more realistic and scalable way, opening new possibilities for studying disease-linked genes in more realistic and predictive ways.

Pera focused on a gene called DYRK1A, which plays a key role in brain development and is associated with conditions like autism, microcephaly, and intellectual disability. He introduced the same DYRK1A mutation into iPSCs from each mouse strain and coaxed those stem cells to form neurons. Despite having the exact same genetic change, the neurons responded very differently depending on their genetic background. Some looked like healthy human brain cells. Others resembled neurons seen in patients with autism or microcephaly.

A new stem cell–based platform developed at JAX is shedding light on one of the biggest mysteries in genetics: why the same disease-causing mutation can affect people in dramatically different ways—from severe symptoms to no symptoms at all.🧪 🧫 🧠 🔬

https://go.jax.org/stem-cells-autism

Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development Zygotic genome activation (ZGA) failure leads to developmental arrest and poses a clinical challenge to women’s fertility. We observed that human embryos arresting at the eight-cell ZGA stage exhibite...

Out now in @science.org Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development | Science www.science.org/doi/10.1126/...

First preprint of the year! New work from @jimmy-ly.bsky.social revealing unexpected roles for 5' UTR length in controlling alternate translational isoforms - important implications for both physiological cell function and rare disease. Small changes -> big impacts.

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

Genomic stop codon scanning reveals quantitative principles of nonsense-mediated mRNA decay Nonsense-mediated mRNA decay (NMD) degrades transcripts containing premature termination codons (PTCs), critically shaping the disease outcomes of protein-truncating variants. While existing NMD rules...

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

Figure 2. Key figure. Possible functional consequences of alternative isoforms.

"Beyond the Gene: Decoding Alternative Isoforms"
by Kaia Mattioli (@kaiamattioli.bsky.social) & Martha Bulyk

"The degree to which alternative isoforms actually contribute to the complexity of the human proteome in their endogenous contexts has been the subject of much debate..."

shorturl.at/YbNoB

I heard this story from Scott Kennedy a few years back. This is very cool. The war between TEs and host genomes continues!

Gene regulation through exon junction complex modularity - Nature Structural & Molecular Biology This Review summarizes the various functions of the exon junction complex in RNA splicing and beyond, to influence gene regulation.

Nice Review #EJC

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

If you’re into RBPs, miRNAs, RNA regulation, or love cool new tech in biology…You don’t want to miss the talk of @dmitry-kretov.bsky.social (@ulaval.ca) the creator of RBPscan, a powerful method to quantitatively map RNA–protein interactions inside living cells; Wed 10th at 16:30 online.

Viral RNA blocks circularization to evade host codon usage control - Nature Rather than adapting to the codon usage of their host, viruses use viral 5′ untranslated regions to initiate translation, which allows them to produce viral proteins in host cells efficiently despite ...

Very interesting paper from Yi Liu's lab. Translation initiation regulation through 5' UTR can turn off codon usage effects in viruses. Adds to previous work in field that codon usage control feeds back to translation initiation www.nature.com/articles/s41...

How does messenger RNA (mRNA) get out of the nucleus to become a protein? Eukaryotic mRNA is packaged, exported, and then translated in the cytoplasm. But how do these steps work? And what are open questions? Check out our new review for our take: www.annualreviews.org/content/jour... (1/3)

Transcription-induced mutation and gBGC at the Transcriptional Start Site impact the evolution of human protein-coding genes In the human genome, mutation rates vary along genes, yet their fine-scale structure and causes have remained largely unexplored. Here, we map mutations at single-nucleotide resolution, and uncover a ...

Our pre-print on the evolution of nucleotide content at the start of human protein-coding genes is finally out!

In this paper we demonstrate that the nucleotide content at the beginning of human protein-coding genes is greatly impacted by non-adaptive evolution.

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

A graphic explaining how mRNA vaccines work, which was showed to study participants.

Teaching people how mRNA vaccines actually work protects against misconceptions about mRNA vaccination changing the recipient's DNA, without the need to repeat the false claims, according to experiments with over 3,500 participants. In PNAS: https://ow.ly/sVwH50Xzutc

Collective homeostasis of condensation-prone proteins via their mRNAs - Nature The authors discover a homeostatic process termed interstasis, in which an increased concentration of proteins within RNA–protein condensates induces the sequestration of their own mRNAs.

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

KATMAP infers splicing factor activity and regulatory targets from knockdown data - Nature Biotechnology A biophysical model uses knockdown or overexpression data to infer splicing factor activity.

KATMAP infers splicing factor activity and regulatory targets from knockdown data - @daspliceisright.bsky.social go.nature.com/47ycrMJ

New JAX-led course gives early career researchers a front-row seat to personalized cancer care Genomic tumor boards connect early career researchers with real-world cancer cases and clinical decision-making

🧬 Translating lab discoveries into patient care is complex. Early-career scientists often lack access to clinical context, making it challenging to connect research w/ patient outcomes.

Our virtual course offers exposure to clinical decision-making in #PrecisionOncology: www.jax.org/news-and-ins...

Strong promoters are mutationally robust Mutational robustness is the persistence of a phenotype upon mutation. It facilitates molecular evolution and has been characterized in a variety of biological systems, but studies of prokaryotic prom...

A fun little side project I've been working on with @stepadenisov.bsky.social , Mato Lagator, and Andreas Wagner: "Strong promoters are mutationally robust". Briefly...

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

Connecting research and clinical practice: training the next generation of translational scientists - Nature Biotechnology A virtual course provides an opportunity for early-career researchers to witness the translation of basic and preclinical research to inform clinical decisions related to precision oncology.

Connecting research and clinical practice: training the next generation of translational scientists - @jacksonlab.bsky.social @jaxeducation.bsky.social go.nature.com/4qlnjEI

mRNA poly(A)-tail length is a battleground for coronavirus–host competition Most eukaryotic mRNAs contain a poly(A) tail, which in post-embryonic cells enhances their stability. Many cytoplasmic RNA viruses also harbor poly(A) tails on their genomic RNA and mRNAs. Here, we re...

Check out the latest work from our lab, led by Arash Latifkar @ara-latifkar.bsky.social , www.biorxiv.org/content/10.1...

Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer Pancreatic ductal adenocarcinoma (PDAC) remains a devastating malignancy characterized by limited therapeutic options for advanced disease. Immunotherapy, in particular, has had dismal success rates i...

Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against #PancreaticCancer 🧪 www.biorxiv.org/content/10.1...