About

Britt Glaunsinger is a Professor of Molecular and Cell Biology and a Professor of Plant and Microbial Biology at the University of California, Berkeley. She holds the Class of 1963 Chair and is an associated faculty member at the Center for Computational Biology. Her research focuses on computational biology, with particular interests in areas such as AI/Machine Learning for Biology, Computational Biophysics and Systems Biology, Computational Epidemiology and Infectious Disease Modeling, and Computational and Statistical Genomics. She is involved in training and mentoring students, including PhD students like Sahil Shah, and contributes to the academic community through her role as a PhD Co-Advisor. Her contact email is glaunsinger@berkeley.edu, and her lab webpage provides further information about her work.

Research topics

• Virology
• Biology
• Medicine
• Pathology
• Immunology
• Political Science
• Genetics
• Cell biology

Selected publications

• Cytoplasmic mRNA decay by the antiviral nuclease RNase L promotes transcriptional repression

  Cell Reports · 2026-02-25

  articleOpen accessSenior author

  Ribonuclease (RNase) L is an antiviral factor that promiscuously degrades viral and cellular RNA in the cytoplasm. This results in extensive translational reprogramming, altering mRNA processing and export. Here, we reveal that another major consequence of cytoplasmic RNase L activity is the repression of nascent RNA synthesis in the nucleus. This is not associated with altered nuclear RNA stability but instead results from transcriptional repression. For RNA polymerase II, repression is primarily associated with reduced occupancy of serine-2-phosphorylated polymerase in gene bodies, indicating an elongation defect. Prominent among the transcriptionally downregulated loci are immune-related genes, supporting a role for RNase L in tempering innate immune and inflammatory responses. RNase L activation also caused disruption of nucleoli and reduced RNA polymerase I and III transcription. Crosstalk between RNA decay and transcription thereby contributes to the large-scale modulation of gene expression in RNase L-activated cells.

  PublisherDOI

• Cleavage of the RNA polymerase II general transcription factor TFIIB tunes transcription during stress

  Genes & Development · 2026-05-13

  preprintOpen accessSenior author

  Cellular stressors often cause widespread repression of RNA polymerase II (RNAP II) activity, which is thought to facilitate a focused transcriptional output toward stress resolution. In many cases, however, the underlying regulatory mechanisms remain unknown. Here, we demonstrate that stress-induced downregulation of the general transcription factor TFIIB tempers expression of specific stimulus response genes. Following a variety of stressors, TFIIB is proteolytically cleaved between its cyclin folds at conserved aspartic acid residue D207 by caspase-3 and caspase-7. Cleavage in this portion of the protein significantly reduces the ability of TFIIB to form a TBP-TFIIB-DNA promoter complex in vitro. Using both overexpression and endogenous base editing, we found that B and T cells that are unable to cleave TFIIB upregulate expression of a select gene set during apoptosis. These TFIIB-sensitive genes are primarily short, stimulus-responsive, and proto-oncogenic loci, and cleavage of TFIIB temporally restricts their expression. Failure to cleave TFIIB during stress leads to aberrant lymphocyte proliferation during chemical perturbation. Hence, caspase targeting of TFIIB destabilizes transcription to tune gene expression, allowing for proper stress resolution.

  PublisherDOI

• RNA polymerase III transcription-associated polyadenylation promotes the accumulation of noncoding retrotransposons during infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-16 · 1 citations

  preprintOpen accessSenior authorCorresponding

  The accumulation of RNA Polymerase III (Pol III) transcribed short interspersed nuclear element (SINE) retrotransposon RNA is a hallmark of various cellular stressors, including DNA virus infection. However, the molecular mechanisms driving the induction of these normally repressed loci are largely undefined. Here, we reveal that in addition to Pol III transcriptional induction, gammaherpesvirus infection stimulates mRNA-like 3' end processing of SINE RNAs that leads to their stabilization. We developed a convolutional neural network (CNN)-based model that identified a polyadenylation-associated motif as the key hallmark of infection-induced SINEs. Indeed, mRNA polyadenylation machinery is recruited in a Pol III-dependent manner to virus-induced loci, including B2 SINE and tRNA genes. Infection causes enhanced polyadenylation of SINE ncRNA, which is required for its stable accumulation. This virus-host interaction therefore highlights an inducible, coupled relationship between Pol III transcription and mRNA-like polyadenylation. It also reveals that co-option of the polyadenylation machinery by Pol III is a mechanism to increase the abundance of noncoding RNA during pathogenic stress. SIGNIFICANCE: Short interspersed nuclear elements (SINEs) are hyperabundant and transcribed by RNA polymerase III (Pol III) to produce noncoding retrotransposons. Although generally not detectable in healthy somatic cells, SINE RNA expression is upregulated during stress, including viral infection and inflammatory diseases. We used gammaherpesvirus infection to uncover pathways leading to increased SINE RNA expression. Using a newly developed deep learning model and genomics analyses, we reveal that infection-induced accumulation of SINEs is driven by increased Pol III transcription and Pol III-dependent recruitment of polyadenylation machinery. This stimulates polyadenylation of SINEs, which is a known stabilizer of these noncoding transcripts. Our findings suggest that inducible alterations to Pol III transcript 3' end processing modulate the abundance of noncoding retrotransposons during pathogenic stress.

  PublisherOA PDFDOI

• The Kaposi’s sarcoma-associated herpesvirus TBP mimic uses a noncanonical DNA-binding mode to promote viral late gene transcription

  Nucleic Acids Research · 2025-10-14

  articleOpen accessSenior author

  Kaposi's sarcoma-associated herpesvirus (KSHV) orchestrates late gene transcription through viral transcriptional activators that hijack host RNA polymerase II (RNAPII) machinery, maintaining selectivity for viral promoters. Among these, the KSHV protein ORF24 serves as a TATA-binding protein (TBP) mimic essential for recognizing viral late promoters, although the molecular mechanisms underlying its function remain poorly characterized. Here, we used AlphaFold3 to predict the structure of ORF24 in complex with DNA and validated key features in both transfected cells and during KSHV lytic replication. Structural modeling revealed that ORF24 employs a noncanonical DNA-binding mode where the C-terminal domain (CTD) makes critical DNA contacts beyond the canonical TBP fold. Targeted mutagenesis confirmed that ORF24 requires conserved TBP-like phenylalanines alongside a polar-rich binding interface distinct from cellular TBP. During infection, both the TBP-like domain and CTD are essential for ORF24 occupancy at viral late promoters. Most surprisingly, we discovered that ORF24 pre-assembles with RNAPII and the viral protein ORF34 to achieve stable promoter binding. This cooperative assembly mechanism represents a fundamental departure from stepwise eukaryotic transcription initiation, resembling a prokaryotic strategy within the eukaryotic nucleus.

  PublisherDOI

• Cytoplasmic mRNA decay by the anti-viral nuclease RNase L promotes transcriptional repression

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-08

  preprintOpen accessSenior authorCorresponding

  Ribonuclease (RNase) L is an antiviral factor that promiscuously degrades viral and cellular RNA in the cytoplasm. This causes extensive translational reprogramming and alters mRNA processing and export. Here, we reveal that another major consequence of cytoplasmic RNase L activity is the repression of nascent RNA synthesis in the nucleus. This is not associated with altered nuclear RNA stability but instead results from a global loss of RNA polymerase II (Pol II) occupancy across the genome. Prominent among the transcriptionally downregulated loci are immune-related genes, supporting a role for RNase L in tempering innate immune and inflammatory responses. These transcriptional changes are associated with reduced levels and altered localization of a portion of serine 5-phosphorylated Pol II into nuclear speckles. Crosstalk between RNA decay and transcription thereby contributes to the large-scale modulation of gene expression in RNase L-activated cells.

  PublisherOA PDFDOI

• SP140–RESIST pathway regulates interferon mRNA stability and antiviral immunity

  Nature · 2025-06-11 · 14 citations

  articleOpen access

  Abstract Type I interferons are essential for antiviral immunity 1 but must be tightly regulated 2 . The conserved transcriptional repressor SP140 inhibits interferon-β ( Ifnb1 ) expression through an unknown mechanism 3,4 . Here we report that SP140 does not directly repress Ifnb1 transcription. Instead, SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of a previously uncharacterized regulator that we call RESIST (regulated stimulator of interferon via stabilization of transcript; previously annotated as annexin 2 receptor). RESIST promotes Ifnb1 mRNA stability by counteracting Ifnb1 mRNA destabilization mediated by the tristetraprolin (TTP) family of RNA-binding proteins and the CCR4–NOT deadenylase complex. SP140 localizes within punctate structures called nuclear bodies that have important roles in silencing DNA-virus gene expression in the nucleus 3 . Consistent with this observation, we find that SP140 inhibits replication of the gammaherpesvirus MHV68. The antiviral activity of SP140 is independent of its ability to regulate Ifnb1 . Our results establish dual antiviral and interferon regulatory functions for SP140. We propose that SP140 and RESIST participate in antiviral effector-triggered immunity 5,6 .

  PublisherOA PDFDOI

• The Kaposi’s sarcoma-associated herpesvirus TBP mimic uses a non-canonical DNA binding mode to promote viral late gene transcription

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-29

  preprintOpen accessSenior authorCorresponding

  Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) orchestrates late gene transcription through viral transcriptional activators that hijack host RNA polymerase II machinery, maintaining selectivity for viral promoters. Among these, the KSHV protein ORF24 serves as a TATA-binding protein (TBP) mimic essential for recognizing viral late promoters, although the molecular mechanisms underlying its function remain poorly characterized. Here, we used AlphaFold3 to predict the structure of ORF24 in complex with DNA and validated key features in both transfected cells and during KSHV lytic replication. Structural modeling revealed that ORF24 employs a non-canonical DNA binding mode where the C-terminal domain (CTD) makes critical DNA contacts beyond the canonical TBP fold. Targeted mutagenesis confirmed that ORF24 requires conserved TBP-like phenylalanines alongside a polar-rich binding interface distinct from cellular TBP. During infection, both the TBP-like domain and CTD are essential for ORF24 occupancy at viral late promoters. Most surprisingly, we discovered that ORF24 pre-assembles with RNA polymerase II and the viral protein ORF34 to achieve stable promoter binding. This cooperative assembly mechanism represents a fundamental departure from stepwise eukaryotic transcription initiation, resembling a prokaryotic strategy within the eukaryotic nucleus. Summary Bullet points The structure of the KSHV TBP mimic ORF24 binding DNA was modeled and experimentally tested. KSHV ORF24 uses an extended DNA-binding interface beyond the canonical TBP fold. ORF24 requires cooperative pre-assembly with transcriptional machinery before DNA engagement

  PublisherOA PDFDOI

• Cleavage of the RNA polymerase II general transcription factor TFIIB tunes transcription during stress

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-28 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Cellular stressors often cause widespread repression of RNA polymerase II (RNAP II) activity, which is thought to facilitate a focused transcriptional output towards stress resolution. In many cases, however, the underlying regulatory mechanisms remain unknown. Here, we demonstrate that stress-induced downregulation of the general transcription factor TFIIB tunes the expression of specific stress response genes. In response to a variety of stressors, TFIIB is proteolytically cleaved at a conserved aspartic acid residue by caspases 3 and 7. Using both overexpression and endogenous base-editing, we find that B and T cells that are unable to cleave TFIIB fail to appropriately dampen transcription of short, stimulus-responsive and proto-oncogenic genes. The promoters of TFIIB-sensitive genes are bound by TFIIB and RNAP II, although their transcription is restrained until stimulated by stress. Subsequently, their expression is modulated through TFIIB cleavage. We further demonstrate that stress-induced TFIIB cleavage prevents aberrant lymphocyte proliferation and suppresses transcription from a pathogenic gammaherpesvirus. Hence, caspase targeting of TFIIB destabilizes transcription to tune gene expression, allowing for proper stress resolution.

  PublisherDOI

• RNA polymerase III transcription-associated polyadenylation promotes the accumulation of noncoding retrotransposons during infection.

  PubMed · 2025-08-12 · 1 citations

  articleOpen accessSenior author

  The accumulation of RNA Polymerase III (Pol III) transcribed short interspersed nuclear element (SINE) retrotransposon RNA is a hallmark of various cellular stressors, including DNA virus infection. However, the molecular mechanisms driving the induction of these normally repressed loci are largely undefined. Here, we reveal that in addition to Pol III transcriptional induction, gammaherpesvirus infection stimulates mRNA-like 3' end processing of SINE RNAs that leads to their stabilization. We developed a convolutional neural network (CNN)-based model that identified a polyadenylation-associated motif as the key hallmark of infection-induced SINEs. Indeed, mRNA polyadenylation machinery is recruited in a Pol III-dependent manner to virus-induced loci, including B2 SINE and tRNA genes. Infection causes enhanced polyadenylation of SINE ncRNA, which is required for its stable accumulation. This virus-host interaction therefore highlights an inducible, coupled relationship between Pol III transcription and mRNA-like polyadenylation. It also reveals that co-option of the polyadenylation machinery by Pol III is a mechanism to increase the abundance of noncoding RNA during pathogenic stress.

  PublisherOA PDFDOI

• Spatiotemporal regulation of the Kaposi’s sarcoma-associated herpesvirus host shutoff factor SOX

  2025-05-16

  preprintOpen accessSenior author

  Kaposi’s sarcoma-associated herpesvirus (KSHV) employs multiple strategies to manipulate host cell biology during lytic replication, among which host shutoff (HSO) plays a critical role in evading immune detection and remodeling the intracellular environment to favor viral gene expression. Central to this process is the protein SOX (shutoff and exonuclease), a bifunctional nuclease with both DNA exonuclease activity and endonucleolytic cleavage activity against host and viral mRNAs. While SOX has been characterized as an essential effector of host shutoff, relatively little is known about the regulation of SOX itself. This work provides an investigation of SOX expression patterns during lytic KSHV infection and explores emerging evidence that KSHV, like other viruses, may regulate SOX protein abundance and activity to balance viral replication with host shutoff.

  PublisherOA PDFDOI

Recent grants

• Functional Characterization of Herpesvirus-Activated Noncoding Retrotransposon RNAs

  NIH · $423k · 2019–2021

• NIH Grant K01CA117982

  NIH · $778k · 2012

• Disruption of Cellular RNA Processing by Kaposi's Sarcoma-Associated Herpesvirus

  NIH · $5.8M · 2010–2030

• Regulation of Gammaherpesviral Late Gene Expression

  NIH · $3.8M · 2015–2026

• NIH Grant R01CA160556

  NIH · $1.5M · 2017

Frequent coauthors

• Jamie H. D. Cate

  University of California, Berkeley

  33 shared

• Ella Hartenian

  University of Lausanne

  32 shared

• Allison L. Didychuk

  University of California, Berkeley

  30 shared

• John Karijolich

  Vanderbilt University

  22 shared

• Jessica M. Tucker

  University of Iowa

  20 shared

• Eva Nogales

  Howard Hughes Medical Institute

  18 shared

• Stephanie N. Gates

  University of Michigan–Ann Arbor

  18 shared

• Andreas Martin

  18 shared

Labs

• Center for Computational BiologyPI