I'm very excited to announce my official appointment as Chair of the Department of Systems Biology at Columbia @columbiauniversity.bsky.social @columbiamed.bsky.social @columbiasysbio.bsky.social. Looking forward to more SysBio growth in NY!
systemsbiology.columbia.edu
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...
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)
Not in the microprotein field that I know of. But definitely some interesting work in recent years like this one www.science.org/doi/10.1126/...
Proteins are like the characters in a book: they are essential, but most of the information in the book lies not in the characters themselves, but in the plots - how they develop, interact, and drive the story - much like the regulatory information encoded in noncoding DNA.
While we often think genes to be like RPS5 with almost exclusive coding conservation, there is also IL6 with the opposite pattern (although its coding DNA is likely still functional). Most genes are in between. In the end noncoding DNA dominates conserved DNA because the huge imbalance: 98% vs 2%.
Why do I believe noncoding DNA carry more genetic information than coding DNA in the human genome? One argument beyond our MYC data: >70% of the conserved DNA are noncoding. While a lack of conservation does not mean lack of function, the presence of conservation often indicates function.
Thanks! That’s exactly the question we’re trying to answer in ongoing work. We’re currently testing several candidate RNA-binding proteins. It may be related to the TIS granule described by Christine Mayr’s group. Any suggestions are very welcome!
agreed. I meant 'common misunderstanding of the centric dogma as protein-centric'
most pol2 transcripts likely do not require microRNA processing to terminate. but I agree that pre-mRNAs, and even mRNAs that are not being translated, could have moonlighting functions just like lncRNAs
Most of the credit goes to co–1st authors
Peiguo Shi and FeiyueYang for their awesome team work. Also thank all co-authors esp Tala from Jianwen Que lab, as well as for valuable feedback from Chaolin Zhang lab, Sara Zaccara lab, and Columbia_CGP
Imaging reveals altered mRNA & protein localization when the element is disrupted. Encoding a short lived nuclear protein with a short-lived mRNA, MYC is translated perinuclearly to enter the nucleus fast & before being degraded. The ultraconserved element is required for this.
yet RNA-seq reveals MYC target genes as the most down-regulated gene set when the ultraconserved element was blocked with three different ASOs, compared to non-targeting control ASOs, suggesting MYC function loss without change in protein abundance
the phenotype of the unannotated ultraconserved site is validated using mutations in bulk and clonal cells, mutations on plasmids, & steric blocking ASOs, all resulting in cell growth defect. However, there is no change in mRNA or protein abundance, using qPCR/RNA-seq and 5 different MYC antibodies
while the ultraconserced site with a positive phenotype can be explained by overlapping seed match sites of two tumor suppressor microRNAs, the other ultraconserved site, has no predicted functions
the biggest surprise is the 3' UTR, where the strongest positive phenotype and the strongest negative phenotype map to two adjacent sites, the only two ultraconserved elements (perfectly conserved in 82 verterbrates) in the locus, separated by a highly conserved RNA stem loop
Paradoxically, phenotypic impact of noncoding seqs correlates inversely with conservation, esp. in promoter. This is inline with reports showing rapid evolution of cis-regulatory elements. Our fitness measurement does correlate with human lineage-specific constraints, but weakly
We mapped the fitness landscape of the 10kb MYC locus using SpRY-Cas9 saturation mutagenesis. 67% of the essential bps are noncoding. So even for a protein coding gene locus, most genetic information may be encoded outside of coding regions.
The protein centric view of the central dogma, ie genetic information flows from DNA to RNA to protein, completely ignores info in noncoding seqs. But > 70% conserved seqs are noncoding. We need unbiased experimental evidence, including functional annotation of noncoding seqs.
Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...
Thanks John!
#ScienCV useful tips below. also you can drag to re-order Products list
Research Briefing featuring our work @natcardiovascres.nature.com : Hotspot RPL3L variants drive early onset heart failure through a dual mechanism
www.nature.com/articles/s44...
Excited to publish our work on how mutations in the muscle-specific ribosomal protein RPL3L drive severe heart disease. This is Part I of a larger body of work led by Michael - stay tuned for Part II on how specialized ribosomes function in normal physiology www.nature.com/articles/s44...
We are thrilled to share our latest work uncovering the mechanistic basis of target-directed microRNA degradation (TDMD). This work was driven by @jakobfarnung.bsky.social and @elenaslo.bsky.social in a fantastic collaboration with Brenda Schulman's lab. tinyurl.com/E3TDMD (1/5)
📢 Our Dept. of Systems Biology at Columbia University has an open tenure-track Assistant Professor position in the broad area of quantitative biology. Come join our awesome department in NYC! Please circulate.
apply.interfolio.com/177622
Suggested deadline: 12/15/2025.
@columbiasysbio.bsky.social
Check out the latest study from our lab, led by @mhall98.bsky.social :
www.biorxiv.org/content/10.1... (1/2)
It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.
very interesting work on ribosome cooperativity
wonder if we should replace 'coding' with 'canonical', i.e., lncRNA = long non-canonical RNA, as compared to long canonical RNA (mRNA)
