Another set of uORF impact mutations very likely to be causal in this set (uORFs - changes in UTR sequences which make or destroy an upstream ORF - uORF - often key for regulation)
New Publication:
Whole Genome Sequencing of "Mutation-Negative" Individuals With Cornelia de Lange Syndrome
@uoe-igc.bsky.social
doi.org/10.1155/humu...
Whole Genome Sequencing of "Mutation-Negative" Individuals With Cornelia de Lange Syndrome
@uoe-igc.bsky.social
doi.org/10.1155/humu...
Whole Genome Sequencing of “Mutation‐Negative” Individuals With Cornelia de Lange Syndrome
This study was aimed at assessing the diagnostic utility of whole genome sequence analysis in a well-characterised research cohort of individuals referred with a clinical suspicion of Cornelia de Lan....
doi.org
July 29, 2025 at 12:19 PM
Another set of uORF impact mutations very likely to be causal in this set (uORFs - changes in UTR sequences which make or destroy an upstream ORF - uORF - often key for regulation)
A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics
elifesciences.org/articles/101...
elifesciences.org/articles/101...
A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics
An upstream open-reading frame in Escherichia coli regulates expression of the downstream genes in response to diverse translation stresses.
elifesciences.org
June 3, 2025 at 7:05 AM
A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics
elifesciences.org/articles/101...
elifesciences.org/articles/101...
An uORF-encoded mobile peptide sparks systemic stomatal immunity: Cell www.cell.com/cell/fulltex...
An uORF-encoded mobile peptide sparks systemic stomatal immunity
In Arabidopsis, the uORF-encoded long-distance mobile peptide USIC in pathogen-infected
local leaves activates systemic stomatal immunity, leading to stomatal closure in
uninfected distal leaves.
www.cell.com
January 28, 2026 at 4:41 AM
An uORF-encoded mobile peptide sparks systemic stomatal immunity: Cell www.cell.com/cell/fulltex...
Lost in Translation...
Nishii et al show that thermospermine-dependent thiolation of tRNA is important for #xylem development as it influences upstream open reading frame (uORF)-mediated translational control of key developmental regulators
doi.org/10.1093/pcp/...
#PlantDevelopment
#PlantScience
Nishii et al show that thermospermine-dependent thiolation of tRNA is important for #xylem development as it influences upstream open reading frame (uORF)-mediated translational control of key developmental regulators
doi.org/10.1093/pcp/...
#PlantDevelopment
#PlantScience
September 25, 2026 at 12:27 PM
Lost in Translation...
Nishii et al show that thermospermine-dependent thiolation of tRNA is important for #xylem development as it influences upstream open reading frame (uORF)-mediated translational control of key developmental regulators
doi.org/10.1093/pcp/...
#PlantDevelopment
#PlantScience
Nishii et al show that thermospermine-dependent thiolation of tRNA is important for #xylem development as it influences upstream open reading frame (uORF)-mediated translational control of key developmental regulators
doi.org/10.1093/pcp/...
#PlantDevelopment
#PlantScience
Functional analysis of TTN uORFs shows that translational regulation is context dependent.
tinyurl.com/TTNuORF
1. TTN uORF disruption increased luciferase reporter expression. 👍
2. Endogenous TTN uORF editing using CRISPR/CAS-9 in iPSC-CMs did not increase titin protein. ❌
tinyurl.com/TTNuORF
1. TTN uORF disruption increased luciferase reporter expression. 👍
2. Endogenous TTN uORF editing using CRISPR/CAS-9 in iPSC-CMs did not increase titin protein. ❌
September 16, 2026 at 8:22 AM
Functional analysis of TTN uORFs shows that translational regulation is context dependent.
tinyurl.com/TTNuORF
1. TTN uORF disruption increased luciferase reporter expression. 👍
2. Endogenous TTN uORF editing using CRISPR/CAS-9 in iPSC-CMs did not increase titin protein. ❌
tinyurl.com/TTNuORF
1. TTN uORF disruption increased luciferase reporter expression. 👍
2. Endogenous TTN uORF editing using CRISPR/CAS-9 in iPSC-CMs did not increase titin protein. ❌
Latest research from my group. We activated BDNF protein expression by disrupting a repressive uORF using a CRISPR base editing strategy: www.sciencedirect.com/science/arti...
#OxfordPaediatrics #IDRMOxford #BDNF #uORF #CRISPR #BaseEditing
#OxfordPaediatrics #IDRMOxford #BDNF #uORF #CRISPR #BaseEditing
Targeted BDNF upregulation via upstream open reading frame disruption
To understand the relative contributions of 5ʹ UTR elements to translation output, we performed a comprehensive analysis of upstream open reading fram…
www.sciencedirect.com
January 6, 2026 at 4:36 PM
Latest research from my group. We activated BDNF protein expression by disrupting a repressive uORF using a CRISPR base editing strategy: www.sciencedirect.com/science/arti...
#OxfordPaediatrics #IDRMOxford #BDNF #uORF #CRISPR #BaseEditing
#OxfordPaediatrics #IDRMOxford #BDNF #uORF #CRISPR #BaseEditing
Ribo-seq and RNA-seq data identified a uORF-containing TTN 5' UTR which was found to be highly expressed and has strong uORF ribosome occupancy.
September 16, 2026 at 8:22 AM
Ribo-seq and RNA-seq data identified a uORF-containing TTN 5' UTR which was found to be highly expressed and has strong uORF ribosome occupancy.
Congratulations to our Sectional Pitch Master Dr. Whitney Besse for winning 1st place at the 2025 Yale Life Science PitchFest live pitch session for her project PKD1 UORF-Blocking ASOs as Therapy for ADPKD!!
So impressed, so proud!! @yaleventures.bsky.social
So impressed, so proud!! @yaleventures.bsky.social
December 9, 2025 at 11:34 PM
Congratulations to our Sectional Pitch Master Dr. Whitney Besse for winning 1st place at the 2025 Yale Life Science PitchFest live pitch session for her project PKD1 UORF-Blocking ASOs as Therapy for ADPKD!!
So impressed, so proud!! @yaleventures.bsky.social
So impressed, so proud!! @yaleventures.bsky.social
HIV-1 uses a non-AUG uORF for protein translation, activating a specific T cell response and modulating transcript expression. Fascinating insights into viral strategy! #HIVResearch PMID:39966383, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-56772-3 #Medsky #Pharmsky #RNA 🧪
Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression | Nature Communications
Human immunodeficiency virus type-1 (HIV-1) is a complex retrovirus that relies on alternative splicing, translational, and post-translational mechanisms to produce over 15 functional proteins from its single ~10 kb transcriptional unit. Using ribosome profiling, nascent protein labeling, RNA sequencing, and whole-proteomics of infected CD4 + T lymphocytes, we characterized the transcriptional, translational, and post-translational landscape during infection. While viral infection exerts a significant impact on host transcript abundance, global translation rates are only modestly affected. Proteomics data reveal extensive transcriptional and post-translational regulation, with many genes showing opposing trends between transcript/ribosome profiling and protein abundance. These findings highlight a complex regulatory network orchestrating gene expression at multiple levels. Viral ribosome profiling further uncovered extensive non-AUG translation of small peptides from upstream open read
doi.org
March 17, 2025 at 12:10 AM
HIV-1 uses a non-AUG uORF for protein translation, activating a specific T cell response and modulating transcript expression. Fascinating insights into viral strategy! #HIVResearch PMID:39966383, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-56772-3 #Medsky #Pharmsky #RNA 🧪
Mapping #CRISPR activity patterns with GRACE. In vivo gene editing sometimes happens at unexpected places. Reporters, such as GRACE, light up the cells that have been mutated. Flies are at @vdrc-flies.bsky.social and plasmids @addgene.bsky.social
Described here:
www.nature.com/articles/s41...
Described here:
www.nature.com/articles/s41...
March 31, 2026 at 7:15 AM
Mapping #CRISPR activity patterns with GRACE. In vivo gene editing sometimes happens at unexpected places. Reporters, such as GRACE, light up the cells that have been mutated. Flies are at @vdrc-flies.bsky.social and plasmids @addgene.bsky.social
Described here:
www.nature.com/articles/s41...
Described here:
www.nature.com/articles/s41...
A µORF controls translation (and transcription) of the type II topAI/yjhQ toxin antitoxin module which is induced under various ribosome-targeting ATB!
elifesciences.org/reviewed-pre...
elifesciences.org/reviewed-pre...
A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics
elifesciences.org
April 29, 2025 at 7:07 AM
A µORF controls translation (and transcription) of the type II topAI/yjhQ toxin antitoxin module which is induced under various ribosome-targeting ATB!
elifesciences.org/reviewed-pre...
elifesciences.org/reviewed-pre...
Thrilled to share that our paper is finally out in Science Advances!
We uncovered how a uORF-encoded microprotein can control mitochondrial biology and lipid metabolism in brown fat. So proud of this work! www.science.org/doi/10.1126/...
We uncovered how a uORF-encoded microprotein can control mitochondrial biology and lipid metabolism in brown fat. So proud of this work! www.science.org/doi/10.1126/...
Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice
A uORF-encoded microprotein, SLC35A4-MP, modulates mitochondrial morphology and function in brown adipose tissue.
www.science.org
August 29, 2025 at 8:23 PM
Thrilled to share that our paper is finally out in Science Advances!
We uncovered how a uORF-encoded microprotein can control mitochondrial biology and lipid metabolism in brown fat. So proud of this work! www.science.org/doi/10.1126/...
We uncovered how a uORF-encoded microprotein can control mitochondrial biology and lipid metabolism in brown fat. So proud of this work! www.science.org/doi/10.1126/...
Plant Science Research Weekly June 27 2025 plantae.org/plant-scienc... (3/3) Elucidation and recreation of the biosynthetic pathway for taxol; ABA2 uORF regulates germination timing; A phosphorylation switch balances growth and stress response in cotton
June 27, 2025 at 6:53 AM
Plant Science Research Weekly June 27 2025 plantae.org/plant-scienc... (3/3) Elucidation and recreation of the biosynthetic pathway for taxol; ABA2 uORF regulates germination timing; A phosphorylation switch balances growth and stress response in cotton
Excited our work featured in latest Molecular Cell issue. Q: How do senescent cells respond to stress? A: #Senescence suppresses the ISR by inhibited uORF bypass on ATF4 #RNA due to #ribosome reduction. This activates a remodeled secretory phenotype. www.cell.com/molecular-ce...
Senescence suppresses the integrated stress response and activates a stress-remodeled secretory phenotype
Payea et al. find that ribosome depletion associated with senescence suppresses the
integrated stress response (ISR) and leads to transcriptional remodeling of the senescence
secretome. Stress-induced...
www.cell.com
November 22, 2024 at 4:19 AM
Excited our work featured in latest Molecular Cell issue. Q: How do senescent cells respond to stress? A: #Senescence suppresses the ISR by inhibited uORF bypass on ATF4 #RNA due to #ribosome reduction. This activates a remodeled secretory phenotype. www.cell.com/molecular-ce...
For example, the 5′-UTR of the CKS2 RNA populates two conformations, one promoting increased translation of a uORF, and one reducing translation of the main ORF. (7/n)
July 27, 2025 at 5:03 PM
For example, the 5′-UTR of the CKS2 RNA populates two conformations, one promoting increased translation of a uORF, and one reducing translation of the main ORF. (7/n)
ME: Anyway, what I'm proposing here is a slight orthographic reform to make spelled-out numbers follow alphabetical order, like this: One, Two, Twree, Uorf, Vive, Ziks, Ziven, Zöight, Zyne, Zzen.
WOMAN NAMED MIRIAM WEBSTER ON OUR FIRST DATE: Is this why you swept right
WOMAN NAMED MIRIAM WEBSTER ON OUR FIRST DATE: Is this why you swept right
March 21, 2025 at 8:23 PM
ME: Anyway, what I'm proposing here is a slight orthographic reform to make spelled-out numbers follow alphabetical order, like this: One, Two, Twree, Uorf, Vive, Ziks, Ziven, Zöight, Zyne, Zzen.
WOMAN NAMED MIRIAM WEBSTER ON OUR FIRST DATE: Is this why you swept right
WOMAN NAMED MIRIAM WEBSTER ON OUR FIRST DATE: Is this why you swept right
Cool new work explaining the dynamics of mRNA translation with the ribosome to inhibit SG localization- by the Moon Lab
#ribosomes #uORF #mRNATranslation #StressResponse
genesdev.cshlp.org/content/earl...
#ribosomes #uORF #mRNATranslation #StressResponse
genesdev.cshlp.org/content/earl...
Ribosome association inhibits stress-induced gene mRNA localization to stress granules
A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields
genesdev.cshlp.org
May 15, 2025 at 2:00 PM
Cool new work explaining the dynamics of mRNA translation with the ribosome to inhibit SG localization- by the Moon Lab
#ribosomes #uORF #mRNATranslation #StressResponse
genesdev.cshlp.org/content/earl...
#ribosomes #uORF #mRNATranslation #StressResponse
genesdev.cshlp.org/content/earl...
Happy to announce publication of a collaboration between my group, Neelam Sen's lab and Alan Hinnebusch at NAR combining FACS-uORF (MPRA) and Ribo-seq to clarify how Ded1 enhances mRNA translation. Great team effort! academic.oup.com/nar/article/...
Suppression of upstream ORF translation is not a widespread mechanism of translational stimulation by yeast helicase Ded1
Abstract. Ded1 is an essential DEAD-box helicase in yeast that broadly stimulates translation initiation and is critical for messenger RNAs (mRNAs) with st
academic.oup.com
May 7, 2026 at 3:10 PM
Happy to announce publication of a collaboration between my group, Neelam Sen's lab and Alan Hinnebusch at NAR combining FACS-uORF (MPRA) and Ribo-seq to clarify how Ded1 enhances mRNA translation. Great team effort! academic.oup.com/nar/article/...
Our latest work on HIV-1 translational control is out!
@naturecomms.bsky.social
www.nature.com/articles/s41...
Here, we performed a transcriptomics, translatomics and whole proteomics analysis during the course of infection.
@lbmcinlyon.bsky.social
@ensdelyon.bsky.social
@inserm.fr
@naturecomms.bsky.social
www.nature.com/articles/s41...
Here, we performed a transcriptomics, translatomics and whole proteomics analysis during the course of infection.
@lbmcinlyon.bsky.social
@ensdelyon.bsky.social
@inserm.fr
Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression - Nature Communications
Here, integrating ribosome profiling, RNA-seq and proteomics to reveal transcriptional and post-translational regulation in HIV-infected T cells, the authors show that non-AUG translation of viral ups...
www.nature.com
February 18, 2025 at 2:08 PM
Our latest work on HIV-1 translational control is out!
@naturecomms.bsky.social
www.nature.com/articles/s41...
Here, we performed a transcriptomics, translatomics and whole proteomics analysis during the course of infection.
@lbmcinlyon.bsky.social
@ensdelyon.bsky.social
@inserm.fr
@naturecomms.bsky.social
www.nature.com/articles/s41...
Here, we performed a transcriptomics, translatomics and whole proteomics analysis during the course of infection.
@lbmcinlyon.bsky.social
@ensdelyon.bsky.social
@inserm.fr
Oh we have a whole consortium about this! Likely some number of bifunctional lncRNA/ microprotein RNAs. Also, many small ORFs are regulatory though on a lncRNA that might be less intuitive than a uORF. Some folks think ribosomes stabilize lncRNAs as a job.
🔎 #microproteins
🔎 #microproteins
November 13, 2024 at 12:12 PM
Oh we have a whole consortium about this! Likely some number of bifunctional lncRNA/ microprotein RNAs. Also, many small ORFs are regulatory though on a lncRNA that might be less intuitive than a uORF. Some folks think ribosomes stabilize lncRNAs as a job.
🔎 #microproteins
🔎 #microproteins
Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control https://www.biorxiv.org/content/10.1101/2024.11.20.624465v1
Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control https://www.biorxiv.org/content/10.1101/2024.11.20.624465v1
Initiation of translation on eukaryotic mRNAs requires a 40S ribosome loaded with an initiator tRNA
www.biorxiv.org
November 21, 2024 at 3:18 AM
Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control https://www.biorxiv.org/content/10.1101/2024.11.20.624465v1
Now online! An uORF-encoded mobile peptide sparks systemic stomatal immunity
An uORF-encoded mobile peptide sparks systemic stomatal immunity
In Arabidopsis, the uORF-encoded long-distance mobile peptide USIC in pathogen-infected local leaves activates systemic stomatal immunity, leading to stomatal closure in uninfected distal leaves.
dlvr.it
January 28, 2026 at 1:42 PM
Now online! An uORF-encoded mobile peptide sparks systemic stomatal immunity
Scientists reveal PKCη as a driver of #TNBC #metastasis by suppressing Hippo signaling & activating YAP, while a uORF-encoded peptide degrades PKCη, highlighting a novel therapeutic vulnerability in aggressive #BreastCancer.
#OpenAccess in #STTT: doi.org/10.1038/s413...
#OpenAccess in #STTT: doi.org/10.1038/s413...
March 9, 2026 at 4:25 PM
Scientists reveal PKCη as a driver of #TNBC #metastasis by suppressing Hippo signaling & activating YAP, while a uORF-encoded peptide degrades PKCη, highlighting a novel therapeutic vulnerability in aggressive #BreastCancer.
#OpenAccess in #STTT: doi.org/10.1038/s413...
#OpenAccess in #STTT: doi.org/10.1038/s413...
