McManus Lab at CMU

@mcmanuslabrna.bsky.social

Excited to share our newest work! We asked whether RNA molecules need to be in a specific place in the cell to do their job. We found that a single RNA must reach the midbody, the structure that pinches two dividing cells apart, for cell division to finish efficiently. 🧵⬇️

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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...

Probing RNA-protein interactions in the early mouse embryo

The union of two germ cells to form a zygote, and subsequent early embryo development, are marked by radical remodeling of virtually every major class of biomolecules as the specialized germline states give way to the rapid and active growth that marks early development. In recent years, advances in ultra-low input genome-wide methods have enabled systematic analyses of mRNA abundance, and of chromatin organization, throughout early development in a variety of model systems. Here, we extend these efforts to the study of RNA binding protein (RBP) function in early mouse embryos, adapting REMORA 1 -- based on fusing an RNA-editing enzyme to an RBP of interest -- for use in early embryos. We benchmark our approach for several well-studied RBPs, successfully recovering expected features of their RNA cargos, and assayed the RNA cargos for 17 RBPs of interest for early gene regulation. Analysis of changes in mRNA metabolism following knockdowns of the RBPs surveyed here allowed us to identify direct regulatory functions for a subset of RBPs in the early mammalian embryo, including an unanticipated role for the RNA export adaptor Alyref in control of 3 prime polyadenylation sites. Together, our data provide a proof of concept resource for systematically exploring RBP functions in mammalian embryogenesis. ### Competing Interest Statement The authors have declared no competing interest. Eunice Kennedy Shriver National Institute of Child Health and Human Development, https://ror.org/04byxyr05, NIHR01HD099816

doi.org

This preprint from Helen Sakharova is one of the coolest things to come out of my lab: “Protein language models reveal evolutionary constraints on synonymous codon choice.” Codon choice is a big puzzle in how information is encoded in genomes, and we have a new angle. www.biorxiv.org/content/10.1...

Protein language models reveal evolutionary constraints on synonymous codon choice

Evolution has shaped the genetic code, with subtle pressures leading to preferences for some synonymous codons over others. Codons are translated at different speeds by the ribosome, imposing constrai...

biorxiv.org

These are amazing stories. Lucy Shapiro is one of my scientific heroes, Steve McKnight has made such fundamental contributions to many fields, and triple drug therapies for CF represent an amazing story in chemical biology and protein folding and I often teach this to undergrads.

Bede Portz@ysptsps.bsky.social · last yr.

Major Medical Prizes Given to Cell Biology and Cystic Fibrosis Pioneers www.nytimes.com/2025/09/11/h...