Amazing insight from David Brow @bmolchem.bsky.social on potential mechanisms of U6 snRNA dysfunction in retinitis pigmentosa! Plus a potential therapeutic strategy based on some classic nucleic acid biochemistry experiments and competing RNA structures.
rnajournal.cshlp.org/content/earl...
IRES-TrAPPr provides a new gold standard for high-throughput IRES research.
✅ Quantifies CDI vs IRES translation in parallel
✅ Screens hundreds of viral & human IRESes at once
✅ Temporal resolution for stress-response studies
✅ Avoids promoter and splice sites artifacts that make false-positives
Importantly, >1,000 short human & viral IRES candidates nominated in prior DNA-based screens had no IRES activity compared to CDI in IRES-TrAPPr. These are likely artifacts that occur from cryptic promoters & splice sites in DNA-based IRES assays. (4/5)
After validating IRES-TrAPPr with structure / function analyses of viral IRESes, we screened IRES elements from hundreds of viruses and found that viral IRESes from warm-blooded hosts may have evolved higher structural stability to maintain folding at higher temperatures. (3/5)
We built IRES-TrAPPr, an RNA-based massively parallel reporter assay that simultaneously measures cap-dependent AND IRES-driven translation from thousands of co-transfected mRNAs - all in one experiment. (2/5)
Check out our new preprint www.biorxiv.org/content/10.6...)! Most human mRNAs recruit ribosomes by cap-dependent initiation (CDI). But during viral infection & cell stress, CDI gets inhibited. So how do mRNAs keep translating? Viruses use IRESes, but do human genes? (1/5) #RNA #virology #IRES
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/...
Hey, wouldja look at that! An incredible one man show from Pablo Bora, an amazing postdoc...we used Steven Floor's beautiful REMORA approach (fusing RNA base editors to RBPs, allowing RBP cargo to be identified by edits) to explore RBP-RNA binding in mouse embryos
doi: doi.org/10.64898/202...
Major new work by the #TransCODE Consortium out today in @nature.com.
Read all about our efforts to shed light onto the forgotten areas of the human proteome. #Microproteins #Peptideins #DarkProteome
This was a huge global collaboration, in part funded via #NIH
www.nature.com/articles/s41...
1/
Massive and important positive news...
#NSF #GRFP awards are out.
2,599 awards!
+
1,440 Honorable Mentions.
A significant boost from last year.
Congratulations to the winners (and HM-s)!
& many thanks to the reviewers & program officers who made this possible.
www.research.gov/grfp/Awardee...