2025

adaptive variation in mutagenesis driven by protein self-assembly

SSRN (PRE-PRINT)

Van Elgort, A., Jakobson, C.M., Byers, J.S.*, Futia, R.A.*, Chen, Y.R., Lozanoski, T.M., Harvey, Z.H., Xie, J.L., Garcia, D.M., Jarosz, D.F.‡

Protein self-assembly, common among DNA replication and repair factors, can materialize epigenetic memory that tunes rates of genome diversification to expand adaptive opportunities.

2024

Combining Nanopore direct RNA sequencing with genetics and mass spectrometry for analysis of T-loop base modifications across 42 yeast tRNA isoacceptors

nucleic acids research

Shaw, E.A.*, Thomas, N.K.*, Jones, J.D., Abu-Shumays, R.L., Vaaler, A.L., Akeson, M., Koutmou, K.S., Jain, M.‡, Garcia, D.M.‡

Nanopore sequencing and mass spectrometry of all cytosolic tRNA isoacceptors from S. cerevisiae permitted detailed analysis of conserved modification in the T-loop and their interdependencies.

2022

Biochemical principles in prion-based inheritance (review)

epigenomes

Dennis E.M., Garcia, D.M.

2021

a prion accelerates proliferation at the expense of lifespan

elifE

Garcia, D.M.*‡, Campbell, E.A.*, Jakobson, C.M., Tsuchiya, M., Shaw, E.A., DiNardo, A.L., Kaeberlein, M., Jarosz, D.F.‡

A highly conserved RNA-modifying enzyme, the pseudouridine synthase Pus4/TruB, can act as a prion, endowing yeast with greater proliferation, increased cell size, and altered translation, at the cost of shortened lifespan.

• eLife Press Pack: How proteins help yeast adapt to changing conditions

2020

a non-amyloid prion particle that activates a heritable gene expression program

molecular cell

Chakravarty, A.K., Smejkal, T., Itakura, A., Garcia, D.M., Jarosz, D.F.

Discovered that phase separation of an evolutionary ancient RNA-binding protein allows it to act as a protein-based genetic element. 

2016

A common bacterial metabolite elicits prion-based bypass of glucose repression

eLife

Garcia, D.M.*, Dietrich, D.*, Clardy, J.‡, Jarosz, D.F.‡

Activity-guided fractionation identified the first bacterial metabolite that potently induces a prion in nature. Demonstrated that chemically simple and ubiquitous small molecules can induce epigenetic states. Also finally explained a mysterious observation first made by Louis Pasteur over 140 years ago.

• eLife Insight: An acid tale of prion formation. Tuite, M.F., eLife 2016, 5:e22256

• Editor’s Choice: Bacteria stop fermentation with lactic acid. Science Signaling  9,457: ec288

• Stanford Medicine Scope: How prions help yeast feast. Spector, R., December 1, 2016

2016

Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits

Cell

Chakrabortee, S.*, Byers, J.S.*, Jones, S., Garcia, D.M., Bhullar, B., Chang, A., She, R., Lee, L., Fremin, B., Lindquist, S.‡, Jarosz, D.F.‡

Defined a new class of non-amyloid prions in yeast responsible for protein-based transgenerational inheritance that do not rely necessarily on stable protein aggregates like classic (amyloid) prions.

• Remembering the Past: A New Form of Protein-Based Inheritance. Tuite, M.F., Cell 167, 369–381

• Science Daily: Revising the meaning of ‘prion’. October 4, 2016

• Stanford Medicine Scope: DNA dethroned? Spector, R., October 6, 2016

2014

Rebels with a cause: molecular features and physiological consequences of yeast prions (Review)

FEMS Yeast Research

Garcia, D.M. and Jarosz, D.F.

2011

Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs

Nature Structural and Molecular Biology

Garcia, D.M.*, Baek, D.*, Shin, C., Bell, G.W., Grimson, A., Bartel, D.P. 

Discovered new sequence features central to the microRNA pathway, an ancient and widespread mechanism of post-transcriptional gene control. Results were integrated into miRNA target prediction program TargetScan.org, used by tens of thousands of users per month.