About

Nicholas Ingolia is a Professor of Molecular & Cell Biology at the Center for Computational Biology. His research focuses on gene expression and regulation, genomics and genetics, network and systems biology, and RNA biology. He is involved in training students through the Designated Emphasis program, working with students such as Anna Freitas and Jin Young Kim. As a principal investigator, he contributes to advancing understanding in these fields through his research and mentorship.

Research topics

• Genetics
• Biology
• Computational biology
• Cell biology

Selected publications

• Metabolic stress reveals widespread accumulation of cap-unmethylated RNAs

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-24

  articleOpen access

  G), a conserved modification essential for mRNA function. Although traditionally viewed as constitutive, we developed a mass spectrometry-based method to demonstrate that in both yeast and mammalian cells, a substantial population of mRNAs lack cap methylation in response to SAM-limiting conditions and oxidative stress, which may be frequently encountered across organisms. Through developing two transcriptome-wide approaches, we found that methylation is enriched on specific transcripts and uncovered an unexpected connection between histone H3K36me3 and cap methylation, with both marks preferentially associated with stress-responsive MAPK signaling pathways. Strikingly, cap-unmethylated mRNAs exhibit features of canonical mRNAs-they are polyadenylated, exported to the cytosol, and translated. Enforced cap methylation reduces cell growth under SAM limitation, suggesting that unmethylated mRNAs confer an adaptive advantage during stress. These findings establish mRNA cap methylation as a dynamic, regulated modification and a previously underappreciated layer of gene expression control.

  PublisherDOI

• Translation elongation as a rate-limiting step of protein production

  Cell Systems · 2026-02-01

  article
  PublisherDOI

• BPS2026 – Deciphering disordered regions controlling mRNA decay in high-throughput

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Calcium-dependent synaptic proteomics reveals EGFR signaling at active synapses

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-21

  article

  Synapses are dynamic structures whose protein composition remodels in response to activity. These activity-dependent processes shape synaptic maturation and plasticity, enabling the development and adaptation of neural circuits. However, defining the molecular basis of activity-dependent synaptic remodeling remains challenging because active synapses are sparse and transient, and current proteomic approaches cannot selectively label proteins at these sites. To address this, we took advantage of activity-driven calcium transients and developed a synapse-targeted calcium-dependent biotin ligase (synaptic Cal-ID). Using synaptic Cal-ID, we examined the activity-dependent synaptic proteome in cultured neurons and mouse brains. We identified two previously uncharacterized synaptic proteins, Anks1a and Ubash3b. Both proteins are rapidly recruited to synapses in response to activity, where they cooperatively promote EGF receptor (EGFR) accumulation and signaling at synapses to support synaptic maturation. Together, these results establish activity-dependent EGFR signaling as a crucial mechanism linking synaptic activity to synaptic remodeling and maturation. More broadly, our findings highlight a molecular mechanism by which calcium-dependent activity rapidly reorganizes key signaling machinery at active synapses to dynamically regulate local synaptic signaling.

  PublisherDOI

• Precise measurement of molecular phenotypes with barcode-based CRISPRi systems

  Genome biology · 2025-05-25 · 1 citations

  articleOpen accessSenior author

  Genome-wide CRISPR-Cas9 screens have untangled regulatory networks driving diverse biological processes. Their success relies on interrogating specific molecular phenotypes and distinguishing key regulators from background effects. Here, we realize these goals by optimizing CRISPR interference with barcoded expression reporter sequencing (CiBER-seq) to dramatically improve the sensitivity and scope of genome-wide screens. We systematically address technical factors that distort phenotypic measurements by normalizing expression reporters against closely matched promoters. We use our improved CiBER-seq to accurately capture known components of well-studied RNA and protein quality control systems. These results demonstrate the precision and versatility of CiBER-seq for dissecting cellular pathways.

  PublisherOA PDFDOI

• eIF3 engages with 3’-UTR termini of highly translated mRNAs

  eLife · 2025-01-29 · 1 citations

  articleOpen access

  Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3’ untranslated region (3’-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3’-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3’-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling, but not with translational efficiency. The results presented here show that eIF3 engages with 3’-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation.

  PublisherDOI

• Deciphering disordered regions controlling mRNA decay in high-throughput

  Nature · 2025-04-23 · 8 citations

  articleSenior author
  PublisherDOI

• Author response: eIF3 engages with 3’-UTR termini of highly translated mRNAs

  2025-01-29

  peer-reviewOpen access
  PublisherDOI

• Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression

  Molecular Cell · 2024-06-01 · 10 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Author response: eIF3 engages with 3’-UTR termini of highly translated mRNAs

  2024-11-07

  peer-reviewOpen access

  Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3’ untranslated region (3’-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3’-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3’-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling. The results presented here show that eIF3 engages with 3’-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation.

  PublisherDOI

Recent grants

• NIH Grant DP2CA195768

  NIH · $2.4M · 2019

• Functional genomics of the dynamic molecular network controlling mRNA translation and decay

  NIH · $1.2M · 2019–2023

• High-precision pooled screening for quantitative molecular phenotypes

  NIH · $1.2M · 2020–2024

• NIH Grant F32GM080853

  NIH · $117k · 2010

• NIH Grant R21ES022575

  NIH · $428k · 2016

Frequent coauthors

• Jonathan S. Weissman

  Whitehead Institute for Biomedical Research

  121 shared

• Jamie H. D. Cate

  University of California, Berkeley

  69 shared

• Gloria A. Brar

  QB3

  52 shared

• Eric W. Mills

  Massachusetts General Hospital

  44 shared

• Shintaro Iwasaki

  Pioneer (Japan)

  38 shared

• Lucas Ferguson

  University of California, Berkeley

  34 shared

• Alexander Marson

  University of California, San Francisco

  30 shared

• Zuriah A. Meacham

  24 shared

Labs

• Center for Computational BiologyPI

Education

• Ph.D., Molecular & Cell Biology

  Harvard University

  2006

• S.B., Mathematics

  Massachusetts Institute of Technology

  2000

• S.B., Biology

  Massachusetts Institute of Technology

  2000