About

Dr. Aaron Goldstrohm is a Professor in the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota. He is also a member of the Masonic Cancer Center, focusing on the Genetic Mechanisms of Cancer. Raised on a farm in western Pennsylvania, Dr. Goldstrohm developed an early interest in nature, biology, and science, nurtured by an inspiring high school science teacher and participation in prestigious research programs such as the Pennsylvania Governor’s School for Agricultural Sciences and the Howard Hughes Summer Institute. He completed his undergraduate studies in Biochemistry and Molecular Biology at Penn State University, conducting research in Dr. Ross Hardison's laboratory. He earned his graduate degree at Duke University under Dr. Mariano Garcia-Blanco, studying mechanisms regulating mRNA synthesis and processing. Subsequently, he conducted postdoctoral research on post-transcriptional gene regulation at the University of Wisconsin – Madison with Dr. Marvin Wickens. In 2008, Dr. Goldstrohm began his independent academic career as an Assistant Professor at the University of Michigan, where he established a research program centered on gene regulation by Pumilio RNA-binding proteins and taught courses in Biochemistry and Molecular Genetics. In 2015, he joined the University of Minnesota, where he continues to investigate mechanisms of gene regulation and their implications for human disease and developmental biology. Dr. Goldstrohm is also dedicated to education, teaching Molecular Genetics and RNA biology, and has served as Director of Graduate Studies in the Biochemistry, Molecular Biology, and Biophysics training program, demonstrating his commitment to training the next generation of scientists and medical professionals.

Research topics

• Genetics
• Cell biology
• Biology
• Computational biology

Selected publications

• Human pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4–NOT deadenylase complex to repress mRNAs

  Journal of Biological Chemistry · 2026-02-13

  articleOpen accessSenior author

  Pumilio proteins are conserved RNA-binding proteins that control mRNAs involved in development, proliferation, and differentiation. Human PUM1 and PUM2 repress targets by recruiting the CCR4-NOT deadenylase complex through a metazoan-specific, intrinsically disordered repression domain (RD3). Here we dissect RD3 using functional assays, protein interaction assays, and crosslinking mass spectrometry. We identify multiple RD3 peptides that are sufficient for repression and binding to the CCR4-NOT complex. Crosslinking reveals numerous mutually exclusive contacts between RD3 and CCR4-NOT, consistent with a multivalent "fuzzy" binding mode in which interactions are not defined by a single sequence or structure. Sequence scrambling shows that the linear amino acid order of RD3 is dispensable, whereas its physicochemical composition, in particular aliphatic and aromatic residues, is essential for repression and CCR4-NOT binding. These findings support a model in which multivalent interactions between intrinsically disordered regions and effector complexes, governed by amino acid composition, underlie robust PUM-mediated repression and exemplify general principles by which intrinsically disordered regions recruit CCR4-NOT to regulate gene expression.

  PublisherOA PDFDOI

• Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to Pumilio-mediated decay

  Nucleic Acids Research · 2026-01-23 · 1 citations

  articleOpen accessSenior author

  The cytoplasmic fate of messenger RNAs (mRNAs) is dictated by the balance of translation and mRNA degradation, governed in part by the 3' poly-adenosine tail and cytoplasmic poly(A)-binding proteins (PABPCs). Deadenylases remove poly(A) to initiate mRNA decay, while sequence-specific RNA-binding factors, including Pumilio proteins (PUM1 and PUM2), modulate these processes. We investigated how human PUM1&2 repress target mRNAs by accelerating their degradation. We found that the poly(A) tail plays a central role in PUM repression, dependent on the interplay of deadenylases and PABPCs. PUM-mediated repression requires the CCR4-NOT deadenylase but not the poly(A) nuclease. PUMs associate with and require PABPC1 and PABPC4 to repress. In the absence of PABPCs, both PUM targets and non-targets become unstable, bypassing PUM control. Increasing PABPC inhibits PUM activity in a concentration-dependent manner by stabilizing poly(A) mRNAs. The results support a Goldilocks principle, wherein PABPC abundance tunes the response of mRNAs to PUM-mediated repression through protection of poly(A) from deadenylation. We propose that this principle may apply to other poly(A) dependent regulatory factors. Variation of PABPC levels across tissues and development suggests physiological relevance for this mechanism.

  PublisherDOI

• RNA-binding is the essential biological function of the <i>Drosophila</i> protein Brat

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-27

  articleOpen accessSenior authorCorresponding

  Abstract Brain tumor (Brat) is a Drosophila TRIM-NHL protein required for embryogenesis and neural stem cell differentiation. Although structural and biochemical studies established that the Brat NHL domain specifically binds RNA, the in vivo requirement for this activity has not been directly tested. Here, we used structure-guided mutagenesis and genome engineering to determine whether RNA recognition is essential for Brat function during development. The direct interaction between Brat’s NHL domain and RNA containing Brat Binding Sites (BBS) can be abolished by alanine substitution of three separate residues on the NHL surface. We introduced these point mutations into the endogenous brat locus by CRISPR-mediated Scarless Gene Editing to generate three independent RNA-binding defective mutant (RBDmt) alleles. Complementation tests demonstrated that each allele behaves as a strong loss-of-function mutation: homozygotes and hemizygotes are inviable, and RBDmt alleles fail to complement classical brat null and hypomorphic alleles. Lethal phase analysis revealed death predominantly during late larval and pupal stages, consistent with known brat alleles. Consistent with the namesake brat phenotype, RBDmt larval brains exhibited widespread expression of neuroblast markers and a marked reduction of neuronal differentiation. In embryos, these alleles failed to complement female sterile brat alleles and recapitulated characteristic abdominal segmentation defects. Finally, RT-qPCR showed increased expression of endogenous Brat target mRNAs in mutant larvae, consistent with loss of Brat-mediated repression. Together, these results demonstrate that direct RNA binding is the essential molecular activity of Brat and that post-transcriptional regulation of Brat target mRNAs underlies its critical roles across development.

  PublisherOA PDFDOI

• Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to RNA-binding protein-directed decay

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-02

  preprintOpen accessSenior authorCorresponding

  The cytoplasmic fate of mRNAs is dictated by the balance of translation and mRNA degradation, governed in part by the 3' poly-adenosine tail and cytoplasmic poly(A)-binding proteins (PABPCs). Deadenylases remove poly(A) to initiate mRNA decay, while sequence-specific RNA-binding factors, including Pumilio proteins (PUM1 and PUM2), modulate these processes. We investigated how human PUM1&2 repress target mRNAs by accelerating their degradation. We found that the poly(A) tail plays a central role in PUM repression, dependent on the interplay of deadenylases and PABPCs. PUM-mediated repression requires the CCR4-NOT deadenylase but not the poly(A) nuclease (PAN). PUMs associate with and require PABPC1 and PABPC4 to repress. In the absence of PABPCs, both PUM targets and non-targets become unstable, bypassing PUM control. Increasing PABPC inhibits PUM activity in a concentration-dependent manner by stabilizing poly(A) mRNAs. Our results establish a Goldilocks principle wherein PABPC abundance tunes the response of mRNAs to regulatory factors through protection of poly(A) from deadenylation. Variation of PABPC levels across tissues and development suggests physiological relevance for this mechanism.

  PublisherOA PDFDOI

• Human Pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4–NOT deadenylase complex to repress mRNAs

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-20

  articleOpen accessSenior authorCorresponding

  Pumilio (PUM) proteins are conserved RNA-binding proteins that control mRNAs involved in development, proliferation, and stem cell differentiation. Human PUM1 and PUM2 repress targets by recruiting the CCR4-NOT deadenylase complex through a metazoan-specific N-terminal repression domain (RD3), which is predicted to be intrinsically disordered. Here we dissect RD3 using cell-based reporter assays, protein interaction assays with recombinant proteins, and crosslinking mass spectrometry. We identify multiple short RD3 peptides that are sufficient for repression and bind directly to the C-terminal NOT module of CCR4-NOT, comprising CNOT1, CNOT2, and CNOT3 subunits. Crosslinking reveals numerous mutually exclusive contacts between RD3 and the NOT module, consistent with a multivalent "fuzzy" binding mode in which interactions are not defined by a single sequence or structure. Sequence scrambling shows that the linear amino acid order of RD3 is dispensable, whereas its physicochemical composition, in particular distributed aliphatic and aromatic residues, is essential for repression and CCR4-NOT binding. These findings support a model in which low-affinity, multivalent interactions between intrinsically disordered regions (IDRs) and effector complexes, governed by amino acid composition rather than precise sequence, underlie robust PUM-mediated repression, and exemplify general principles by which IDRs recruit the CCR4-NOT complex to regulate gene expression.

  PublisherDOI

• Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex

  RNA · 2024-04-16 · 8 citations

  articleOpen accessSenior author

  The sequence-specific RNA-binding protein Pumilio controls Drosophila development; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we utilize knockdown and knockout approaches coupled with RNA-Seq to measure the impact of Pumilio on the transcriptome of Drosophila cells in culture. We also use an improved RNA co-immunoprecipitation method to identify Pumilio-bound mRNAs in Drosophila embryos. Integration of these datasets with the locations of Pumilio binding motifs across the transcriptome reveal novel direct Pumilio target genes involved in neural, muscle, wing, and germ cell development, and cellular proliferation. These genes include components of Wnt, TGF-beta, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. We identify the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pumilio-mediated repression, and observe concordant regulation of Pumilio:CCR4-NOT target mRNAs. Computational modeling reveals that Pumilio binding, binding site number, clustering, and sequence context are important determinants of regulation. In contrast, we show that the responses of direct mRNA targets to Pumilio-mediated repression are not influenced by their content of optimal synonymous codons. Moreover, contrary to a prevailing model, we do not detect a role for CCR4-NOT in the degradation of mRNAs with low codon optimality. Together, the results of this work provide new insights into the Pumilio regulatory network and mechanisms, and the parameters that influence the efficacy of Pumilio-mediated regulation.

  PublisherOA PDFDOI

• Chemi-Northern: a versatile chemiluminescent northern blot method for analysis and quantitation of RNA molecules

  RNA · 2024-01-24 · 11 citations

  articleOpen accessSenior author

  This report describes a chemiluminescence-based detection method for RNAs on northern blots, designated Chemi-Northern. This approach builds on the simplicity and versatility of northern blotting, while dispensing of the need for expensive and cumbersome radioactivity. RNAs are first separated by denaturing gel electrophoresis, transferred to a nylon membrane, and then hybridized to a biotinylated RNA or DNA antisense probe. Streptavidin conjugated with horseradish peroxidase and enhanced chemiluminescence substrate are then used to detect the probe bound to the target RNA. Our results demonstrate the versatility of this method in detecting natural and engineered RNAs expressed in cells, including messenger and noncoding RNAs. We show that Chemi-Northern detection is sensitive and fast, detecting attomole amounts of RNA in as little as 1 sec, with high signal intensity and low background. The dynamic response displays excellent linearity. Using Chemi-Northern, we measure the reproducible, statistically significant reduction of mRNA levels by human sequence-specific RNA-binding proteins, PUM1 and PUM2. Additionally, we measure the interaction of the poly(A) binding protein, PABPC1, with polyadenylated mRNA. Thus, the Chemi-Northern method provides a versatile, simple, and cost-effective method to enable researchers to analyze expression, processing, binding, and decay of RNAs.

  PublisherOA PDFDOI

• The TRIM-NHL RNA-binding protein Brain Tumor coordinately regulates expression of the glycolytic pathway and vacuolar ATPase complex

  Nucleic Acids Research · 2024-10-01 · 2 citations

  articleOpen accessSenior author

  The essential Drosophila RNA-binding protein Brain Tumor (Brat) represses specific genes to control embryogenesis and differentiation of stem cells. In the brain, Brat functions as a tumor suppressor that diminishes neural stem cell proliferation while promoting differentiation. Though important Brat-regulated target mRNAs have been identified in these contexts, the full impact of Brat on gene expression remains to be discovered. Here, we identify the network of Brat-regulated mRNAs by performing RNA sequencing (RNA-seq) following depletion of Brat from cultured cells. We identify 158 mRNAs, with high confidence, that are repressed by Brat. De novo motif analysis identified a functionally enriched RNA motif in the 3' untranslated regions (UTRs) of Brat-repressed mRNAs that matches the biochemically defined Brat binding site. Integrative data analysis revealed a high-confidence list of Brat-repressed and Brat-bound mRNAs containing 3'UTR Brat binding motifs. Our RNA-seq and reporter assays show that multiple 3'UTR motifs promote the strength of Brat repression, whereas motifs in the 5'UTR are not functional. Strikingly, we find that Brat regulates expression of glycolytic enzymes and the vacuolar ATPase complex, providing new insight into its role as a tumor suppressor and the coordination of metabolism and intracellular pH.

  PublisherOA PDFDOI

• Regulation of the Drosophila transcriptome by Pumilio and CCR4-NOT deadenylase

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-08-30

  preprintOpen accessSenior authorCorresponding

  ABSTRACT The sequence-specific RNA-binding protein Pumilio controls development of Drosophila ; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we utilize knockdown and knockout approaches coupled with RNA-Seq to measure the impact of Pumilio on the transcriptome of Drosophila cells. We also used an improved RNA co-immunoprecipitation method to identify Pumilio bound mRNAs in Drosophila embryos. Integration of these datasets with the content of Pumilio binding motifs across the transcriptome revealed novel direct Pumilio target genes involved in neural, muscle, wing, and germ cell development, and cellular proliferation. These genes include components of Wnt, TGF-beta, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. Additionally, we identified the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pumilio-mediated repression, and observed concordant regulation of Pumilio:CCR4-NOT target mRNAs. Computational modeling revealed that Pumilio binding, binding site number, density, and sequence context are important determinants of regulation. Moreover, the content of optimal synonymous codons in target mRNAs exhibits a striking functional relationship to Pumilio and CCR4-NOT regulation, indicating that the inherent translation efficiency and stability of the mRNA modulates their response to these trans-acting regulatory factors. Together, the results of this work provide new insights into the Pumilio regulatory network and mechanisms, and the parameters that influence the efficacy of Pumilio-mediated regulation.

  PublisherOA PDFDOI

• Measuring Poly-Adenosine Tail Length of RNAs by High-Resolution Northern Blotting Coupled with RNase H Cleavage

  Methods in molecular biology · 2023-10-12 · 2 citations

  articleSenior authorCorresponding
  PublisherDOI

Recent grants

• mRNA regulatory functions of the Drosophila TRIM-NHL protein, Brat

  NIH · $1.4M · 2022–2026

• Novel Regulatory Mechanisms of Drosophila Pumilio

  NIH · $2.7M · 2013–2022

Frequent coauthors

• T.M.T. Hall

  National Institutes of Health

  18 shared

• Chase A. Weidmann

  University of Michigan–Ann Arbor

  16 shared

• Mariano A. Garcia‐Blanco

  University of Virginia

  15 shared

• René M. Arvola

  The Ohio State University

  15 shared

• Trista Schagat

  Promega (United States)

  12 shared

• Carlos Suñé

  Instituto de Parasitología y Biomedicina "López - Neyra"

  11 shared

• Peter L. Freddolino

  University of Michigan–Ann Arbor

  10 shared

• Jennifer Bohn

  Rockefeller University

  9 shared

Labs

• Goldstrohm LabPI

  Focus on gene regulation and its impact on human disease and developmental biology.

Education

• B.S., Biochemistry and Molecular Biology

  Penn State University

• Ph.D.

  Duke University

• Other, Post-transcriptional gene regulation

  University of Wisconsin – Madison