Joseph Daniel Puglisi

Translation fidelity mechanisms and their changes in aging

This study measures proteome-wide translation errors in yeast and mouse, finding that fidelity varies by organism and tissue, increases with age in post-mitotic cells, and is regulated by tRNA pool remodeling.

Remodeling of mRNA by eIF4F in human translation initiation

This study uses single-molecule assays to show eIF4F binding and mRNA remodeling during translation initiation, revealing ATP-dependent conformational changes and their role in ribosome loading.

A ribosomal kinetic checkpoint governs selective mRNA recruitment

This study identifies a ribosomal kinetic checkpoint that governs selective mRNA recruitment through a branched pathway involving productive and arrested states.

Decoding the Sequence Requirements for Translation Initiation

The paper defines an extended translation initiation sequence (eTIS) and shows that a deep-learning model trained on eTIS features accurately predicts translation initiation, revealing that the Kozak sequence is not optimal and identifying conserved nucleotides that enhance initiation efficiency.

RNA regulates repeat-associated non-AUG (RAN) translation initiation in C9orf72 FTD/ALS

This study investigates how RNA structure and sequence context influence RAN translation initiation in C9orf72 repeats, revealing a kinetic bottleneck in initiation at near-cognate start codons.

eIF1 and eIF5 dynamically control translation start site fidelity

This study investigates how eIF1 and eIF5 dynamically regulate translation start site fidelity through single-molecule analysis and cell experiments.

A memory of RPS25 loss drives resistance phenotypes

The paper investigates the phenotypic consequences of RPS25 and RACK1 loss in human cells, finding that RPS25 knockout leads to irreversible resistance traits and gene expression rewiring.

Short translational ramp determines efficiency of protein synthesis

The paper shows that a short translational ramp in mRNA's first 5 codons significantly affects protein synthesis efficiency, independent of tRNA abundance or initiation efficiency.