It's all about RNA baby! Ribose found on Bennu
www.nature.com/articles/s41...
03.12.2025 18:22
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It's all about RNA baby! Ribose found on Bennu
www.nature.com/articles/s41...
This paper was a tour de force and would not be possible without he help of so many collaborators like @juanbonifacino.bsky.social and many more. Thank you!!!
Strikingly, the presence of this frameshifted proteoform was necessary for myocardial contraction, as we showed in PLEKHM2-KO cells that required both the WT and frameshifted proteoforms to recover fully, leading to our model
Furthermore, we were able to show that this frameshifted version of PLEKHM2 generated a hyper-active version of this protein, which did not require activation of its canonical activator
Not only did the frameshift exist, it was highly conserved and encoded for an additional alpha-helix domain
Today our journey ends! We were able to find a highly conserved cellular +1 PRF signal in the gene PLEKHM2/SKIP
A few years ago, we published in Nature (nature.com/articles/s41...) detailing this artefact and noting that no true PRF signal existed in humans gave access to two overlapping open reading frames that both encoded something useful like in viruses
However the authors (nature.com/articles/nat...) and others in the field had unfortunately been using a reporter with a malicious splicing artefact, accidentally presenting PRF activity.
PRF is employed widely across viral clades from HIV-1, Sars-COV-2, RSV, Influenza, etc. However, there was always a chase to find the first real case of PRF occurring in a human, cellular gene. And in 2014, researchers believed that had found the first case in CCR5
Programmed Ribosomal Frameshifting (PRF) is a phenomena that has been studied extensively in viruses since the 80s. In short, a single RNA has the ability to code for multiple proteins by 'recoding' the genetic code i.e. having the ribosome change its reading frame mid-elongation
Excited to announce the YAK lab's first paper and the discovery of the FIRST human cellular PRF signal to give access to two overlapping open reading frames (science.org/doi/10.1126/...)! Before we dive in, the story actually begins in a Nature from 11 years ago
Excited to announce that I have been selected to receive a High-Risk, High-Reward grant from the NIH to help support the research our lab does at the intersection of AI and molecular biology to study RNA. Read more about here: news.stanford.edu/stories/2025...
Excited to collaborate and have people join us! Please checkout the lab website above if you are interested!
I'm extremely thrilled to announce that I will be starting as a group leader at Stanford this upcoming fall! My lab will be studying how RNAs exert themselves in the cell to induce a multitude of biological phenomena using ML, cryoEM/ET, and biochemistry!
www.yousufakhan.com
Check out our new preprint on the discovery of a molecular switch in NAC that mediates nascent chain sorting on the ribosome and prevents mitochondrial protein mistargeting by SRP. A great collaboration with the Shan Lab @Caltech and the Qi Lab @UVA: www.biorxiv.org/content/10.1...
Don’t leave us hanging Hiten!
Going deep on 2A peptides:
www.cell.com/cell-reports...
(Trying to pick between GSG:T2A, GSG:P2A, and furin site:GSG:T2A)
PSA = Google Colab Pro free for one year for academic use (US only):
blog.google/outreach-ini...
Key numbers in cell biology
Having a sense of scale helps to think more rigorously and realistically about biological systems.
ICYMI: New online: SNARE disassembly requires Sec18/NSF side loading
Cool paper on bacterial amyloids as protection from predatory bacteria from the Whitely lab at CU Boulder.
There are predatory fungi, so one wonders if a similar system exists in eukaryotes.
www.nature.com/articles/s41...
Thus, any kind of SNARE can be processed universally by this single molecule machine. Check out the paper for more in-depth structural work! (5/5)
Combining in-vivo mass-spec, single molecule FRET, and time resolved cryoEM, we were able to determine that this NSF/Sec18 ring actually splits itself open from the side to accomodate SNAREs, thus completely bypassing any substrate topology issues! (4/5)
The complex that recycles these SNAREs is called NSF/Sec18. However, our mehanistic understanding of how these complex SNARE proteins are pulled through the NSF/Sec18 complex is poor. SNAREs are like a knotted thread that must somehow be threaded by a NSF/Sec18 needle (3/5)
SNARE proteins are the engines for membrane fusion; they cause neurotransmitters to be released in a synpatic cleft all the way to the relase of hormones. After these SNAREs perform their job, they must naturally be recyled and prepared for additional rounds of fusion (2/5)
Sharing some of my PhD work that just came out today.
TLDR; We found a universal mechanism for all the many kinds of SNAREs are processed and recycled by a single molecular machine that is conserved in all eukaryotic life as we know it (1/5)
www.nature.com/articles/s41...
(1/5)
I'm thrilled and honoured to receive the 2025 Lister Prize, along with seven other fantastic biomedical scientists 🔬🦠🧬
This award will enable us to determine high-resolution structures of viral protein synthesis inside infected cells
At left, a reconstruction of the vault cap with C39 symmetry imposed; at right, the reconstruction after identifying the correct symmetry, with the three non-equivalent protomers highlighted.
1/x New story - the structure of the Vault cap, at 2.3Å! Matching a beautiful preprint from @sjorsscheres.bsky.social, we show that the cap of the vault particle has C13 symmetry, in contrast to the 39-fold symmetry of the body. Study lead by talented postdoc @huanli00.bsky.social from my group! ⬇️
Hi Bluesky, just in time for the holidays I am excited to share the latest pre-print from my group! We solved the 3D structure of a mysterious viral RNA that resists degradation by host nucleases. A short 🧵 &link below – please also check out the full video! #RNA #RNAbiology #RNASky #lovevirology
someone said we need a meme
