Liu JF, Hawley BR, Nicholson L, Jaffrey SR. Decoding m6Am by simultaneous transcription-start mapping and methylation quantification. eLife 13:RP104139, 2025.

This paper introduced CROWN-seq, the first quantitative map of m6Am stoichiometry at every start site across the transcriptome. It showed that m6Am raises nascent transcription rates to increase transcript abundance.

Kam CW, Dumelie JG, Ciceri G, Yang WY, Disney MD, Studer L, Jaffrey SR. Sustained epigenetic reactivation in Fragile X neurons with an RNA-binding small molecule. Genes 16:278, 2025.

This paper showed that a small molecule binding the CGG-repeat RNA reverses epigenetic silencing in Fragile X neurons. It is a proof of concept for treating the disease by targeting the repeat RNA.

Linder B, Sharma P, Wu J, Birbaumer T, Eggers C, Murakami S, Ott RE, Fenzl K, Vorgerd H, Erhard F, Jaffrey SR, Leidel S*, Steinmetz LM*. tRNA modifications tune m6A-dependent mRNA decay. Cell 188:3715–3727, 2025.

This paper showed that modifications on tRNAs tune the m6A-dependent mRNA decay pathway during decoding. It revealed a new layer of regulation over m6A function.

Murakami S, Olarerin-George AO, Liu JF, Zaccara S, Hawley B, Jaffrey SR. m6A alters ribosome dynamics to initiate mRNA degradation. Cell 188:3728–3743, 2025.

This paper showed that m6A stalls ribosomes and induces collisions on the mRNA. Those collisions are the likely trigger that activates m6A-dependent degradation.

Hou Q, Oleynikov M, Mei X, Dong L, Hagen T, Jaffrey SR. A portable poison exon for small molecule control of mammalian gene expression. Nature Methods 22:2337–2348, 2025.

This paper built an engineered intron carrying a poison exon that binds acyclovir. Adding the drug switches almost any gene or transgene on or off.

Dumelie JG, Chen Q, Miller D, Attarwala N, Gross SS, Jaffrey SR. Biomolecular condensates create phospholipid-enriched microenvironments. Nature Chemical Biology 20:302–313, 2024.

This paper showed that phase-separated condensates hold a distinct metabolome and are often enriched in phospholipids. The finding recasts condensates as lipid-containing structures and sites where lipid metabolism can occur.

Oleynikov M, Jaffrey SR. RNA tertiary structure and conformational dynamics revealed by BASH MaP. eLife 13:RP98540, 2024.

This paper introduced BASH MaP, which extends DMS probing to the N7 of guanosine to reach RNA tertiary structure and its conformations. It resolved alternative folds of G-quadruplexes and of the Spinach aptamer in cells.

Hagen T, Litke JL, Nasir N, Hou Q, Jaffrey SR. Engineering acyclovir-induced RNA nanodevices for reversible and tunable control of aptamer function. Cell Chemical Biology 31:1827–1838, 2024.

This paper built an acyclovir-regulated aptamer whose function a small molecule turns on and off. The drug tunes the device reversibly to control aptamer and protein function.

Despic V, Jaffrey SR. mRNA ageing shapes the Cap2 methylome in mammalian mRNA. Nature 614:358–366, 2023.

This paper produced the first map of Cap2, an RNA modification located near the mRNA cap, and showed that it is a marker of mRNA age that can also affect translation. When disturbed, Cap2 loss triggers an innate immune pathway important for controlling viral replication.

Passalacqua LFM, Banco MT, Moon JD, Li X, Jaffrey SR, Ferré-D'Amaré AR. Intricate 3D architecture of a DNA mimic of green fluorescent protein. Nature 618:1078–1084, 2023.

This paper solved the structure of Lettuce, revealing DNA folds and interactions not seen before. It explained how DNA can bind and activate the fluorescence of a small molecule.

Passalacqua LFM, Starich MR, Link KA, Wu J, Knutson JR, Tjandra N, Jaffrey SR, Ferré-D'Amaré AR. Co-crystal structures of the fluorogenic aptamer Beetroot show that close homology may not predict similar RNA architecture. Nature Communications 14:2969, 2023.

This paper solved the structure of Beetroot, a dimerizing aptamer that pairs up to switch on fluorescence. It showed that small sequence differences can produce very different RNA folds.

Ries RJ, Pickering BF, Poh HX, Namkoong S, Jaffrey SR. m6A governs length-dependent enrichment of mRNAs in stress granules. Nature Structural & Molecular Biology 30:1525–1535, 2023.

This paper showed that m6A targets mRNAs into stress granules and explains why long mRNAs are enriched there. Long transcripts carry more m6A because of their exon structure, driving their length-dependent recruitment.

Unti MJ, Jaffrey SR. Highly efficient cellular expression of circular mRNA enables prolonged protein expression. Cell Chemical Biology 30:1637–1646, 2023.

This paper engineered cells to make translating circular mRNAs that persist for a long time. The circular mRNAs can be packaged into virus-like particles and delivered to other cells for high protein expression.

Dey SK, Filonov GS, Olarerin-George AO, Jackson BT, Finley LWS, Jaffrey SR. Repurposing an adenine riboswitch into a fluorogenic imaging and sensing tag. Nature Chemical Biology 18:180–190, 2022.

This paper engineered a fluorogenic aptamer from a natural adenine riboswitch, evolving it for high imaging quality in cells. It introduced a library-randomization protocol that varies both sequence and length to enlarge the fluorophore pocket.

Truong L, Kooshapur H, Dey SK, Li X, Tjandra N, Jaffrey SR, Ferré-D'Amaré AR. The fluorescent aptamer Squash extensively repurposes the adenine riboswitch fold. Nature Chemical Biology 18:191–198, 2022.

This paper solved the structure of Squash, a highly stable aptamer that keeps a riboswitch-like fold but rebuilds it to bind its fluorophore. It showed how an existing RNA fold can be repurposed for fluorescence.

Wu J, Svensen N, Song W, Kim H, Zhang S, Li X, Jaffrey SR. Self-assembly of intracellular multivalent RNA complexes using dimeric Corn and Beetroot aptamers. Journal of the American Chemical Society 144:5471–5477, 2022.

This paper used dimeric Corn and Beetroot aptamers to assemble larger, multivalent RNA complexes inside cells. It provided a route to genetically encoded macromolecular RNA structures.

VarnBuhler BS, Moon J, Dey SK, Wu J, Jaffrey SR. Detection of SARS-CoV-2 RNA using a DNA aptamer mimic of green fluorescent protein. ACS Chemical Biology 17:840–853, 2022.

This paper introduced Lettuce, the first DNA mimic of green fluorescent protein. It showed that a DNA aptamer can switch on fluorescence and be used to detect viral RNA rapidly.

Jansens RJJ, Verhamme R, Mirza AH, Olarerin-George A, Van Waesberghe C, Jaffrey SR*, Favoreel HW*. Alphaherpesvirus US3 protein-mediated inhibition of the m6A mRNA methyltransferase complex. Cell Reports 40:111107, 2022.

This paper showed that an alphaherpesvirus protein inhibits the m6A methyltransferase complex. It demonstrated that viruses can control cellular function by targeting the methylation pathway.

Cho S, Lee G, Pickering BF, Jang C, Park J, He L, Mathur L, Kim SS, Jung S, Tang HW, Monette S, Rabinowitz JD, Perrimon N, Jaffrey SR*, Blenis J*. mTORC1 promotes cell growth via m6A-dependent mRNA degradation. Molecular Cell 81:2064–2075, 2021.

This paper showed that mTORC1 controls expression of the m6A writer component WTAP, adjusting m6A levels to regulate MYC and cancer growth. It linked a central growth-signaling pathway to the epitranscriptome.

Moon JD, Wu J, Dey SK, Litke JL, Kim H, Jaffrey SR. Naturally occurring three-way junctions can be repurposed as genetically encoded RNA-based sensors. Cell Chemical Biology 28:1569–1580, 2021.

This paper repurposed natural RNA three-way junctions into metabolite sensors whose stability is switched by binding. The design toggles from unstable to stable to report metabolites in live cells.

Cheng Y, Xie W, Pickering BF, Chu KL, Savino AM, Yang X, Luo H, Nguyen DT, Mo S, Barin E, Velleca A, Rohwetter TM, Patel DJ, Jaffrey SR, Kharas MG. N6-methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation. Cancer Cell 39:958–972, 2021.

This paper showed that m6A drives a phase-separated nuclear body built on the reader YTHDC1. That body alters nuclear mRNA processing and suppresses myeloid differentiation in leukemia.

Cotter KA, Gallon J, Uebersax N, Rubin P, Meyer KD, Piscuoglio S, Jaffrey SR*, Rubin MA*. Mapping of m6A and its regulatory targets in prostate cancer reveals a METTL3-low induction of therapy resistance. Molecular Cancer Research 19:1398–1411, 2021.

This paper mapped m6A and its targets in prostate cancer and found that low METTL3 can drive therapy resistance. It tied m6A control to prostate cancer growth.

Li X, Wu J, Jaffrey SR. Engineering fluorophore recycling in a fluorogenic RNA aptamer. Angewandte Chemie International Edition 60:24153–24161, 2021.

This paper engineered how a fluorophore binds and exchanges in an aptamer to control photobleaching and fluorescence. It produced a fluorogenic aptamer with distinct and markedly improved photophysical properties.

Litke JL, Jaffrey SR. Trans-ligation of RNAs to generate hybrid circular RNAs using highly efficient autocatalytic transcripts. Methods 196:104–112, 2021.

This paper showed that ribozymes can ligate two separate RNAs together in cells. The approach builds larger circular RNAs from smaller precursors.

Li X, Kim H, Litke JL, Wu J, Jaffrey SR. Fluorophore-promoted RNA folding and photostability enable imaging of single Broccoli-tagged mRNAs in live mammalian cells. Angewandte Chemie International Edition 59:4511–4518, 2020.

This paper used virtual screening to find a fluorophore that acts as a chemical chaperone, promoting Broccoli folding and photostability. The gain in brightness enabled imaging of single mRNAs in live cells.

Zaccara S, Jaffrey SR. A unified model for the function of YTHDF proteins in regulating m6A-modified mRNA. Cell 181:1582–1595, 2020.

This paper showed that the YTHDF proteins act redundantly in a single pathway that promotes mRNA degradation, rather than in separate pathways. It established mRNA instability as the major cellular function of m6A.

Li X, Mo L, Litke JL, Dey SK, Suter SR, Jaffrey SR. Imaging intracellular S-adenosylmethionine dynamics in live mammalian cells with a genetically encoded red fluorescent RNA-based sensor. Journal of the American Chemical Society 142:14117–14124, 2020.

This paper used a red fluorogenic aptamer to image S-adenosylmethionine dynamics in live cells. The far-red readout was spectrally separate from common fluorescent proteins, allowing simultaneous imaging.

Xi L, Carroll T, Matos I, Luo JD, Polak L, Pasolli HA, Brüning JC, Jaffrey SR, Fuchs E. m6A RNA methylation impacts fate choices during skin morphogenesis. eLife 9:e56980, 2020.

This paper showed a physiological role for m6A in directing cell-fate choices during skin development. It connected the modification to a specific developmental program.

Mauer J, Sindelar M, Despic V, Guez T, Hawley BR, Vasseur JJ, Rentmeister A, Gross SS, Pellizzoni L, Debart F, Goodarzi H, Jaffrey SR. FTO controls reversible m6Am RNA methylation during snRNA biogenesis. Nature Chemical Biology 15:340–347, 2019.

This paper showed that snRNAs carry m6Am that is dynamically regulated and is a major target of FTO. It introduced the concept of small nuclear RNA epitranscriptomics.

You M, Litke JL, Wu R, Jaffrey SR. Detection of low-abundance metabolites in live cells using an RNA integrator. Cell Chemical Biology 26:471–481, 2019.

This paper built RNAs that self-cleave in response to a metabolite and release fluorescent aptamers as a running tally. The integrator design allowed quantification of very low-abundance metabolites in living cells.

Litke JL, Jaffrey SR. Highly efficient cellular expression of circular RNA aptamers and devices using autocatalytic transcripts. Nature Biotechnology 37:667–675, 2019.

This landmark paper introduced Tornado, which uses Twister ribozymes so a transcript is autocatalytically cleaved and then ligated by the cellular ligase RTCB into a circle. It produces genetically encoded circular RNAs at very high levels and is now widely used for aptamers, transcript editing, and CRISPR tools.

Filonov GS, Song W, Jaffrey SR. Spectral tuning by a single nucleotide controls the fluorescence properties of a fluorogenic aptamer. Biochemistry 58:1560–1564, 2019.

This paper showed that a single-nucleotide change in the local environment around the fluorophore tunes the aptamer's spectrum. This strategy led to the creation of Orange Broccoli and Red Broccoli as new tools for RNA imaging.

Boulias K, Toczydłowska-Socha D, Hawley BR, Liberman-Isakov N, Takashima K, Zaccara S, Guez T, Vasseur JJ, Debart F, Aravind L, Jaffrey SR*, Greer EL*. Identification of the m6Am methyltransferase PCIF1 reveals the location and functions of m6Am in the transcriptome. Molecular Cell 75:631–643, 2019.

This paper discovered PCIF1, the methyltransferase that makes m6Am, defining the writer for this modification. Knockout and knockdown of PCIF1 then showed that m6Am selectively controls specific mRNAs.

Ries RJ, Zaccara S, Klein P, Olarerin-George A, Namkoong S, Pickering BF, Patil DP, Kwak H, Lee JH, Jaffrey SR. m6A enhances the phase separation potential of mRNA. Nature 571:424–428, 2019.

This paper showed that m6A biology is tied to phase-separated condensates, because m6A reader proteins undergo phase separation to act. m6A uses phase separation to route RNAs to stress granules under stress and into P-bodies otherwise.

Wu J, Zaccara S, Khuperkar D, Kim H, Tanenbaum ME, Jaffrey SR. Live imaging of mRNA using RNA-stabilized fluorogenic proteins. Nature Methods 16:862–865, 2019.

This paper introduced RNA-stabilized proteins, using an RNA-controlled degron and the new Pepper aptamer, which binds and inactivates the degron. This approach allowed the creation of RNA-controlled fluorescent proteins that were used for low-background live imaging of RNA in cells.

Kim H, Jaffrey SR. A fluorogenic RNA-based sensor activated by metabolite-induced RNA dimerization. Cell Chemical Biology 26:1725–1731, 2019.

This paper built an RNA sensor in which a small molecule triggers RNA dimerization, read out by the Corn aptamer. It gave a new way to image metabolite dynamics in living cells.

Grozhik AV, Olarerin-George AO, Sindelar M, Li X, Gross SS, Jaffrey SR. Antibody cross-reactivity accounts for widespread appearance of m1A in 5'UTRs. Nature Communications 10:5126, 2019.

This paper showed that earlier maps of m1A were artifacts caused by the nonspecificity of m1A antibodies. It introduced a method for mapping reverse-transcription misincorporations across the transcriptome, showing that m1A and other disruptive modifications are nearly nonexistent in cellular mRNA.

Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, Vasseur JJ, Chen Q, Gross SS, Elemento O, Debart F, Kiledjian M, Jaffrey SR. Reversible methylation of m6Am in the 5' cap controls mRNA stability. Nature 541:371–375, 2017.

This paper showed that FTO acts mainly on m6Am, not m6A, and that m6Am in the 5' cap can influence mRNA levels. It introduced m6Am as a regulatory epitranscriptomic modification.

Song W, Filonov GS, Kim H, Hirsch M, Li X, Moon JD, Jaffrey SR. Imaging RNA polymerase III transcription using a photostable RNA-fluorophore complex. Nature Chemical Biology 13:1187–1194, 2017.

This paper introduced Corn, a red-shifted fluorogenic aptamer built on a fluorophore with extended electron delocalization. It showed that fluorogenic aptamers can be used as highly sensitive real-time indicators of transcriptional activity.

Warner KD, Sjekloća L, Song W, Filonov GS, Jaffrey SR, Ferré-D'Amaré AR. A homodimer interface without base pairs in an RNA mimic of red fluorescent protein. Nature Chemical Biology 13:1195–1201, 2017.

This paper solved the structure of Corn, which forms a homodimer that encapsulates the fluorophore at a shared, high-affinity site. The dimer interface forms without base pairs, an unprecedented dimerizing RNA architecture.

Vu LP, Pickering BF, Cheng Y, Zaccara S, Nguyen D, Minuesa G, Chou T, Chow A, Saletore Y, MacKay M, Schulman J, Famulare C, Patel M, Klimek VM, Garrett-Bakelman FE, Melnick A, Carroll M, Mason CE, Jaffrey SR*, Kharas MG*. The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nature Medicine 23:1369–1376, 2017.

This paper showed that the m6A writer METTL3 controls a specific differentiation program in blood-cell formation and is deregulated in leukemia. It was among the first studies to tie m6A to cancer and helped launch clinical work on m6A enzymes.

Dumelie JG, Jaffrey SR. Defining the location of promoter-associated R-loops at near-nucleotide resolution using bisDRIP-seq. eLife 6:e28306, 2017.

This paper introduced bisDRIP-seq, which chemically modifies the exposed DNA in an R-loop to map R-loops at near-nucleotide resolution. It revealed a different R-loop landscape than antibody-based methods had reported.

Svensen N, Jaffrey SR. Fluorescent RNA aptamers as a tool to study RNA-modifying enzymes. Cell Chemical Biology 23:415–425, 2016. (Best of 2016 issue.)

This paper showed that fluorogenic aptamers can report on RNA-modifying enzymes, using a methylated Broccoli that demethylases act on. It offered a route to screen for demethylase inhibitors.

Svensen N, Jaffrey SR. Peptide synthesis on a next-generation DNA sequencing platform. ChemBioChem 17:1628–1635, 2016.

This paper synthesized RNA from the DNA clusters on an Illumina flow cell, creating massive immobilized RNA sets for RNA-protein binding assays. It even carried out protein synthesis on the flow cell.

Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M, Jaffrey SR. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537:369–373, 2016.

This paper showed that m6A on the long noncoding RNA XIST promotes its transcriptional repression, with YTHDC1 as the key nuclear reader. It was among the first to assign a molecular function to m6A and to identify RBM15 as a component of the m6A writer complex.

Deglincerti A, Liu Y, Colak D, Hengst U, Xu G, Jaffrey SR. Coupled local translation and degradation regulate growth cone collapse. Nature Communications 6:6888, 2015.

This paper showed that local translation and local mRNA degradation are coupled within the growth cone to control its collapse. The paired synthesis and turnover give axons fast, local control over their behavior.

Filonov GS, Kam CW, Song W, Jaffrey SR. In-gel imaging of RNA processing using Broccoli reveals optimal aptamer expression strategies. Chemistry & Biology 22:649–660, 2015.

This paper introduced the F30 scaffold, a genetically encoded RNA scaffold that makes aptamers fold correctly and stay stable. It became a widely used way to express functional aptamers and also enabled in-gel imaging of RNA processing.

You M, Litke JL, Jaffrey SR. Imaging metabolite dynamics in living cells using a Spinach-based riboswitch. PNAS 112:E2756–E2765, 2015.

This paper used natural riboswitch mechanisms to turn Broccoli fluorescence on and off in response to a metabolite. It established a new design strategy for building genetically encoded RNA sensing devices.

Linder B, Grozhik AV, Olarerin-George AO, Meydan C, Mason CE, Jaffrey SR. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nature Methods 12:767–772, 2015.

This paper introduced miCLIP, the first single-nucleotide-resolution map of m6A and m6Am across the transcriptome. It moved the field from peak-level detection to precise, site-level detection.

Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian SB, Jaffrey SR. 5'UTR m6A promotes cap-independent translation. Cell 163:999–1010, 2015.

This paper showed that m6A in the 5'UTR can promote cap-independent translation. It demonstrated that m6A can regulate mRNA function, though the mechanisms by which m6A affects translation remain to be established.

Lundquist MR, Storaska AJ, Liu TC, Larsen SD, Evans T, Neubig RR, Jaffrey SR. Redox modification of nuclear actin by MICAL-2 regulates SRF signaling. Cell 156:563–576, 2014.

This paper showed that the enzyme MICAL-2 oxidizes methionine on nuclear actin, depolymerizing it and freeing the coactivator MRTF-A to activate SRF-driven transcription in response to nerve growth factor. It was the first to link a redox modification of actin to gene expression, and it identified MICAL-2 as the target of a small-molecule inhibitor of this pathway.

Song W, Strack RL, Svensen N, Jaffrey SR. Plug-and-play fluorophores extend the spectral properties of Spinach. Journal of the American Chemical Society 136:1198–1201, 2014.

This paper described a series of fluorophores that can be swapped into the same fluorogenic aptamer to obtain fluorescence in different colors. It expanded the color range available from Spinach for imaging.

Colak D, Zaninovic N, Cohen MS, Rosenwaks Z, Yang WY, Gerhardt J, Disney MD, Jaffrey SR. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in Fragile X syndrome. Science 343:1002–1005, 2014.

In Fragile X syndrome, a trinucleotide-repeat expansion triggers epigenetic silencing once the repeat exceeds about 200 nucleotides. This paper showed that the repeat is transcribed into RNA that hybridizes to its own DNA to form an R-loop that drives the silencing, and it used this mechanism to design a small molecule that reverses silencing by blocking the RNA-DNA complex.

Warner KD, Chen MC, Song W, Strack RL, Thorn A, Jaffrey SR, Ferré-D'Amaré AR. Structural basis for activity of highly efficient RNA mimics of green fluorescent protein. Nature Structural & Molecular Biology 21:658–663, 2014.

This paper solved the structure of Spinach, revealing a G-quadruplex and base-triple that sandwich the fluorophore and switch on its fluorescence. It showed that the aptamer uses mechanisms similar to those of GFP.

Filonov GS, Moon JD, Svensen N, Jaffrey SR. Broccoli: rapid selection of an RNA mimic of green fluorescent protein by fluorescence-based selection and directed evolution. Journal of the American Chemical Society 136:16299–16308, 2014.

This paper introduced Broccoli, an aptamer with improved performance in cells, selected by fluorescence-based directed evolution. It was the first directed evolution platform for RNA aptamers.

Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metabolism 20:1059–1068, 2014.

This paper explained the long-standing mystery of how the WldS protein protects axons, showing that it works by enhancing SIRT3 function in mitochondria. It then used the NAD+ precursor nicotinamide riboside to activate SIRT3 and protect against noise-induced hearing loss.

Colak D, Ji SJ, Porse BT, Jaffrey SR. Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay. Cell 153:1252–1265, 2013.

This paper revealed that mRNA in axons is dynamically degraded by the nonsense-mediated decay pathway, which is activated locally when axons cross the spinal cord midline. The selective activation of mRNA degradation reshapes the axonal transcriptome, allowing axons to change their trajectories after they cross the midline.

Song W, Strack RL, Jaffrey SR. Imaging bacterial protein expression using genetically encoded RNA sensors. Nature Methods 10:873–875, 2013.

This paper built RNA-based sensors that fluoresce when they bind a target protein. This approach enabled real-time imaging of protein expression dynamics in living cells.

Curanovic D, Cohen M, Slagle CE, Singh I, Leslie CS, Jaffrey SR. Transcriptome-wide profiling of stimulus-induced polyadenylation in living cells using a poly(A) trap. Nature Chemical Biology 9:671–673, 2013.

This paper synthesized clickable adenosine analogs that poly(A) polymerases incorporate into new tails. It provided the first way to track where and when polyadenylation is triggered across the transcriptome.

Strack RL, Disney MD, Jaffrey SR. A superfolding Spinach2 reveals the dynamic nature of trinucleotide repeat-containing RNA. Nature Methods 10:1219–1224, 2013.

This paper engineered Spinach2, a superfolding version with markedly improved performance in cells. The improved Spinach was used to tag and track trinucleotide-repeat RNA dynamics and to discover small molecules that disrupt their aggregation.

Walker BA, Hengst U, Kim HJ, Jeon NL, Schmidt EF, Heintz N, Milner TA, Jaffrey SR. Reprogramming axonal behavior by axon-specific viral transduction. Gene Therapy 19:947–955, 2012.

This paper introduced a gene-therapy strategy that delivers RNA selectively into axon terminals to reprogram their local expression. It proposed a route to make injured axons regrow, relevant to spinal cord injury.

Paige JS, Nguyen-Duc T, Song W, Jaffrey SR. Fluorescence imaging of cellular metabolites with RNA. Science 335:1194, 2012.

This paper built RNA sensors that bind a metabolite and switch on Spinach fluorescence. This study introduced RNA-based sensors as a new way to image small molecules in cells, providing a method for live imaging of metabolite dynamics over time.

Ji SJ, Jaffrey SR. Intra-axonal translation of SMAD1/5/8 mediates retrograde regulation of trigeminal ganglia subtype specification. Neuron 74:95–107, 2012.

This paper showed that SMAD transcription factors are translated locally in axon terminals and respond to the local environment. The locally synthesized transcription factors are retrogradely trafficked to the nucleus to specify neuronal identity.

Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 3'UTRs and near stop codons. Cell 149:1635–1646, 2012.

This landmark paper produced the first map of m6A across the transcriptome using MeRIP-seq, showing enrichment near stop codons and in 3'UTRs. It established m6A as a selective, functional modification and launched the field now known as epitranscriptomics.

Paige JS, Wu KY, Jaffrey SR. RNA mimics of green fluorescent protein. Science 333:642–646, 2011.

This paper introduced RNA mimics of green fluorescent protein, the first approach for genetically encoding fluorescence with RNA. The Spinach aptamer binds and switches on an otherwise non-fluorescent dye, giving selective fluorescent labeling of RNA in cells.

Xu G, Shin SY, Jaffrey SR. Chemoenzymatic labeling of protein C-termini for positive selection of C-terminal peptides. ACS Chemical Biology 6:1015–1020, 2011.

This method used an innovative strategy to drive a protease in reverse to label protein C-termini. It enabled selective C-terminal labeling for the first time and provided a way to map protein cleavage sites across the proteome.

Xu G, Paige JS, Jaffrey SR. Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nature Biotechnology 28:868–873, 2010.

This paper introduced ubiquitin-remnant profiling, which uses an antibody against the diGly remnant left on modified lysines after digestion. It became the standard method for site-level ubiquitination mapping, and its reagent is still in wide use today.

Hengst U, Deglincerti A, Kim HJ, Jeon NL, Jaffrey SR. Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein. Nature Cell Biology 11:1024–1030, 2009.

This paper showed that a stimulus triggers local translation of a cell-polarity complex protein within the axon. The local synthesis of this complex is a critical step that drives axon elongation.

Xu G, Shin SY, Jaffrey SR. Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini. PNAS 106:19310–19315, 2009.

This method uses Edman degradation chemistry to label protein N-termini selectively. It enabled the first proteome-wide mapping of N-termini and of protease cleavage sites.

Cox LJ, Hengst U, Gurskaya NG, Lukyanov KA, Jaffrey SR. Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival. Nature Cell Biology 10:149–159, 2008.

This paper showed that CREB mRNA is localized and translated inside axons, then retrogradely trafficked to the cell body. It was among the first to show that a transcription factor is made locally in axons to carry a long-distance survival signal to the nucleus.

Paige JS, Xu G, Stancevic B, Jaffrey SR. Nitrosothiol reactivity profiling identifies S-nitrosylated proteins with unexpected stability. Chemistry & Biology 15:1307–1316, 2008.

This study profiled how readily individual cysteines across the proteome react with an S-nitrosylating compound. It initiated the field of activity-based reactivity profiling and showed that specific cysteines in specific proteins have unusual reactivity.

Wu KY, Hengst U, Macosko E, Cox L, Urquhart E, Jeromin A, Jaffrey SR. Local translation of RhoA regulates growth cone collapse. Nature 436:1020–1024, 2005.

This paper showed that RhoA mRNA is translated locally within axons to control growth cone collapse. It was the first demonstration that an individual localized transcript has a defined functional role in axon guidance, helping establish local translation as a mechanism in the nervous system.

Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH. Protein S-nitrosylation: a physiologic signal for neuronal nitric oxide. Nature Cell Biology 3:193–197, 2001.

This paper introduced the biotin-switch method, which chemically converts a cysteine S-nitrosylation site into a biotin tag for pull-down. It was the first way to detect S-nitrosylated proteins, and the strategy of turning a post-translational modification into an affinity handle became a foundation of chemical proteomics.