About

Roy Parker is a Distinguished Professor and the Cech-Leinwand Endowed Chair of Biochemistry at the University of Colorado Boulder. His research focuses on understanding the expression, location, and function of eukaryotic RNAs and their connection to human disease. His work includes studying RNP granules, which are large assemblies of RNA and protein in eukaryotic cells, and discovering that these granules are formed through promiscuous intermolecular RNA-RNA interactions, suggesting they are analogous to protein aggregates. He has also identified RNA chaperones that limit these interactions, maintaining RNA function, and is investigating the RNA Chaperone Network and its role in neurological diseases. Another key area of his research involves the tau protein, an RNA-binding protein that forms fibrillar aggregates toxic to neurons, contributing to neurodegeneration and dementia. His lab has found that tau aggregates contain RNA and grow off the surface of RNP granules, and is working to understand the biochemical interactions that promote tau fiber growth and how these interactions can be prevented. Additionally, his research explores how the addition and removal of short oligo(A) tails to non-coding RNAs regulate their degradation, with implications for human diseases. His work aims to develop new disease treatments by understanding these molecular pathways.

Research topics

• Biology
• Medicine
• Computer Science
• Virology
• Internal medicine
• Biochemistry
• Cell biology
• Chemistry
• Engineering
• Biophysics
• Molecular biology
• Genetics
• Business
• Computational biology

Selected publications

• School and Community In Situations of Close Proximity: The Question of Small States

  2025-06-11 · 2 citations

  book-chapterSenior author

  Closely knit communities exist throughout the world, and in each country it is possible to identify ‘communities’ that have a significantly different collective characteristic that separates and distinguishes them from other ‘communities’ within the same state. This identifying characteristic, however, not only singles them out from the others, but also frequently associates them with similar, sometimes almost identical communities in other states. It is in this sense that we identify, for example, ethnic groups who, although a minority in the particular national context in which they are found, form part of a larger, far-flung group with whom they share certain distinguishing characteristics such as language, culture, ethnicity or even nationality. Such is the legacy of maritime colonialism and mercantilism, and of associated diasporas, whether one is considering, say, the Pacific Islanders of Auckland or the people of Caribbean heritage in London and other British cities.

  PublisherDOI

• ZNFX1: a multifunctional modulator of the innate immune response

  Frontiers in Immunology · 2025-03-18 · 4 citations

  reviewOpen accessSenior author

  Recent research has identified ZNFX1 as a critical modulator of the innate immune response. Individuals with loss of function mutations in ZNFX1 have chronic inflammation and increased susceptibility to various pathogens. Several potential functions of ZNFX1 have been proposed, including binding double-stranded RNA to activate antiviral innate immunity, inhibiting the NLRP3 inflammasome, and regulating the stability of host mRNAs. Notably, homologs of ZNFX1 are implicated in innate immunity across a wide range of species, including contributing to transgenerational epigenetic inheritance of small RNA-based defense in C. elegans . In this review, we discuss the significance of ZNFX1 and explore the potential underlying mechanisms that govern its diverse functions.

  PublisherDOI

• Regulation of Cajal bodies: Unexpected connection to 60S ribosomes

  The Journal of Cell Biology · 2025-01-03

  articleOpen accessSenior author

  Cajal bodies are essential sites for the biogenesis of small nuclear and nucleolar ribonucleoproteins. In this issue, Courvan and Parker discuss new work from Neugebauer and colleagues (https://doi.org/10.1083/jcb.202305081) that carefully profiles Cajal Body components and finds an unexpected role for 60S ribosomal proteins.

  PublisherOA PDFDOI

• Plans within plans: post-transcriptional regulation governs macrophage responses

  Trends in Immunology · 2025-07-02 · 5 citations

  review
  PublisherDOI

• Protocol for determining the contribution of protein and RNA to condensate organization by permeabilizing and enzyme-treating live U-2 OS cells

  STAR Protocols · 2025-04-10 · 1 citations

  articleOpen accessSenior author

  Ribonucleoprotein granules are comprised of protein and RNA. We present a protocol for querying the relative contribution of protein and RNA interactions to granule organization by permeabilizing and treating cells with proteinase or RNase enzymes. We then detail steps for performing single-molecule fluorescence in situ hybridization (smFISH) on enzyme-treated samples for RNA visualization. Finally, we describe detailed instructions for quantifying results generated with this protocol. This protocol can potentially query the contribution of protein-RNA, protein-protein, and RNA-RNA interactions to the organization of any intracellular granule. For complete details on the use and execution of this protocol, refer to Parker et al. 1 • A protocol for permeabilizing and enzyme-treating cells in culture • Steps for performing smFISH and smiFISH on permeabilized samples • Detailed instructions for quantifying RNA FISH data in degradation experiments Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Ribonucleoprotein granules are comprised of protein and RNA. We present a protocol for querying the relative contribution of protein and RNA interactions to granule organization by permeabilizing and treating cells with proteinase or RNase enzymes. We then detail steps for performing single-molecule fluorescence in situ hybridization (smFISH) on enzyme-treated samples for RNA visualization. Finally, we describe detailed instructions for quantifying results generated with this protocol. This protocol can potentially query the contribution of protein-RNA, protein-protein, and RNA-RNA interactions to the organization of any intracellular granule.

  PublisherDOI

• Polyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation

  Neuron · 2025-09-02 · 6 citations

  articleOpen accessSenior author

  Tau aggregation is a hallmark of several neurodegenerative disorders, and the gain of toxic function of misfolded tau species is linked to pathobiology. Herein, we identified proteins that limit tau aggregation when targeted to tau aggregates by polyserine domains. Polyserine targeting was most effective at mitigating tau aggregation when fused to the vasolin-containing protein (VCP) adaptor protein fas-associated factor family member 2/UBX domain-containing protein 8 (FAF2/UBXD8). Surprisingly, FAF2/UBXD8 suppresses tau aggregation independent of VCP but does require ubiquitination, membrane localization, and a ubiquitin regulator X (UBX) domain. Validation in animal models demonstrated that polyserine-targeted FAF2/UBXD8 rescues tau-induced neurodegeneration in Drosophila. Further, delivery of targeted FAF2/UBXD8 reduced gliosis, seeding capacity, and insoluble tau levels in PS19 tau transgenic mice while improving contextual fear conditioning. Collectively, our findings highlight polyserine as a tau-targeting strategy and identify targeted FAF2/UBXD8 as a potent suppressor of tau pathology.

  PublisherDOI

• DHX36 modulates stress granule assembly independent of recruitment of mRNAs with G-quadruplex sequence motifs

  Nucleic Acids Research · 2025-09-23 · 4 citations

  articleOpen accessSenior author

  Stress granules are RNA-protein condensates that form in response to an increase in untranslating mRNPs (messenger ribonucleoproteins). Stress granules form by the condensation of mRNPs through a combination of protein-protein, protein-RNA, and RNA-RNA interactions. Several reports have suggested that G-rich RNA sequences capable of forming G-quadruplexes (rG4s) promote stress granule formation. Here, we provide three observations arguing that G-tracts do not promote messenger RNA (mRNA) accumulation in stress granules in human osteosarcoma cells. First, we observed no difference in the accumulation in stress granules of reporter mRNAs with and without G-tracts in their 3' UTRs. Second, in U-2 OS cell lines with reduced expression of DHX36, which is thought to unwind G-quadruplexes, the accumulation of endogenous mRNAs was independent of their predicted rG4-forming potential. Third, while mRNAs in stress granules initially appeared to have more rG4 motifs than bulk mRNAs, this effect disappeared when rG4 motif abundance was normalized to mRNA length. However, we observed that in a G3BP1/2 double knockout cell line, which strongly inhibits stress granule formation, reducing DHX36 expression rescued stress granule-like foci formation. This indicates that DHX36 can limit stress granule formation, potentially by unwinding trans-rG4s or limiting other intermolecular RNA-RNA interactions that promote stress granule formation.

  PublisherOA PDFDOI

• Base Composition Influences the Position and Precision of RNA Polymerase II Disassociation in Basal and Perturbed Conditions

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-03

  articleOpen access

  RNA Polymerase II (Pol II) transcribes all protein-coding and many non-protein coding genes in the genome. Pol II transcription termination is crucial for mRNA maturation and, when disrupted, can lead to altered mRNA processing and mRNA export. Termination involves two intertwined processes: pre-mRNA cleavage and Pol II release from the DNA (disassociation). Despite its importance, the exact mechanisms underlying Pol II disassociation from the DNA remain poorly understood. Moreover, under certain cellular stress conditions, there is a partial failure of cleavage, leading to a shift of the position of disassociation further downstream, a phenomenon known as run-on transcription. We performed the first-ever systematic analysis of Pol II termination across cell types and species and provide novel insights into the mechanism of disassociation. Using a probabilistic mixture model to quantify Poll II dynamics across an entire gene body from nascent RNA sequencing data, we discovered that genes have two types of conserved regions near the disassociation site: one characterized by a T-rich region upstream of disassociation, and another characterized by a GC-rich region surrounding disassociation. Strikingly, the GC-rich disassociation regions have more accessible chromatin and higher levels of phospho-threonine 4 on the CTD of Pol II. Additionally, we find that upstream T-rich genes are preferentially affected by perturbations that alter disassociation, including heat-shock, viral infection, kinase inhibition, and arsenic treatment. Thus, our work has determined there are two types of Pol II disassociation regions, which are differentially affected by perturbation of cellular homeostasis.

  PublisherDOI

• Impact of G-tract RNAs and the DHX36 helicase on stress granule composition and formation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-17

  preprintOpen accessSenior authorCorresponding

  Stress granules are RNA-protein condensates that form in response to an increase in untranslating mRNPs. Stress granules form by the condensation of mRNPs through a combination of protein-protein, protein-RNA, and RNA-RNA interactions. Several reports have suggested that G-rich RNA sequences capable of forming G-quadruplexes promote stress granule formation. Here, we provide three observations arguing that G-tracts capable of forming rG4s do not promote mRNAs partitioning into stress granules in human osteosarcoma cells. First, we observed no difference in the accumulation in stress granules of reporter mRNAs with and without G-tracts in their 3' UTRs. Second, in U-2 OS cell lines with reduced DHX36 expression, which is thought to unwind G-quadruplexes, the partitioning of endogenous mRNAs was independent of their predicted rG4-forming potential. Third, while mRNAs in stress granules initially appeared to have a higher probability of forming rG4s than bulk mRNAs, this effect disappeared when rG4 motif abundance was standardized by mRNA length. However, we observe that in a G3BP1/2 double knockout cell line, reducing DHX36 expression rescued stress granule-like foci formation. This indicates that DHX36 can limit stress granule formation, potentially by unwinding trans rG4s, or limiting other intermolecular RNA-RNA interactions that promote stress granule formation.

  PublisherDOI

• Diverse influences on tau aggregation and implications for disease progression

  Genes & Development · 2025-03-20 · 5 citations

  reviewOpen accessSenior author

  Tau is an intrinsically disordered protein that accumulates in fibrillar aggregates in neurodegenerative diseases. The misfolding of tau can be understood as an equilibrium between different states and their propensity to form higher-order fibers, which is affected by several factors. First, modulation of the biochemical state of tau due to ionic conditions, post-translational modifications, cofactors, and interacting molecules or assemblies can affect the formation and structure of tau fibrils. Second, cellular processes impact tau aggregation through modulating stability, clearance, disaggregation, and transport. Third, through interactions with glial cells, the neuronal microenvironment can affect intraneuronal conditions with impacts on tau fibrilization and toxicity. Importantly, tau fibrils propagate through the brain via a "prion-like" manner, contributing to disease progression. This review highlights the biochemical and cellular pathways that modulate tau aggregation and discusses implications for pathobiology and tau-directed therapeutic approaches.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F32GM011479

  NIH · $71k

• NIH Grant T32GM008659

  NIH · $5.5M · 2020

• NIH Grant R37GM045443

  NIH · $3.1M · 2014

• Stress Granules in Yeast and Mammals

  NIH · $4.7M · 1991–2023

Frequent coauthors

• Denise Muhlrad

  University of Colorado Boulder

  97 shared

• Carolyn J. Decker

  University of Colorado Boulder

  77 shared

• James M. Burke

  University of Florida

  59 shared

• Anthony Khong

  University of California, Davis

  54 shared

• Joshua R. Wheeler

  Stanford University

  44 shared

• Evan Lester

  Cornell College

  42 shared

• Haiwei Song

  Agency for Science, Technology and Research

  40 shared

• Ambro van Hoof

  The University of Texas Health Science Center at Houston

  38 shared

Education

• Ph.D.

  University of California, San Francisco

• Other

  University of Massachusetts, Worcester

Awards & honors

• Distinguished Professor, University of Colorado Boulder (201…
• National Academy of Sciences Member (2012)
• President, The RNA Society (2010)
• American Academy of Arts & Sciences Fellow (2010)
• Galileo Fellow (2003)