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  1. Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection.

    Molecular cell · 2026

    Alternative polyadenylation (APA) generates transcript isoforms with distinct 3' ends, yet the repertoire of its protein regulators remains poorly defined. Using a large-scale tethered function screen, we profiled 879 human RNA-binding proteins (RBPs) and identified 63 high-confidence activators of poly(A) …

    PMID 42361791 DOI ↗

  2. Organizing research at scale: Reflections on leading multi-team scientific collaborations.

    Molecular cell · 2026 · 86(3): 434-438

    Collaborations are critical features of modern academic science. As biological problems get more complex, larger teams become necessary. However, there is an increased level of friction in coordinating activities and attributing credit in large-scale scientific collaborations. Simple organizational principles and …

    PMID 41650944 DOI ↗

  3. Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.

    Molecular cell · 2024 · 84(19): 3826-3842.e8

    RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and …

    PMID 39303722 DOI ↗

  4. Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.

    Molecular cell · 2024 · 84(19): 3790-3809.e8

    mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map …

    PMID 39303721 DOI ↗

  5. RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1β- and RNA-dependent co-activator of osteoclast gene expression.

    Molecular cell · 2023 · 83(19): 3421-3437.e11

    The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on histone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor κB (RANK) converts the …

    PMID 37751740 DOI ↗

  6. HydRA: Deep-learning models for predicting RNA-binding capacity from protein interaction association context and protein sequence.

    Molecular cell · 2023 · 83(14): 2595-2611.e11

    RNA-binding proteins (RBPs) control RNA metabolism to orchestrate gene expression and, when dysfunctional, underlie human diseases. Proteome-wide discovery efforts predict thousands of RBP candidates, many of which lack canonical RNA-binding domains (RBDs). Here, we present a hybrid ensemble RBP classifier …

    PMID 37421941 DOI ↗

  7. Proteomic discovery of chemical probes that perturb protein complexes in human cells.

    Molecular cell · 2023 · 83(10): 1725-1742.e12

    Most human proteins lack chemical probes, and several large-scale and generalizable small-molecule binding assays have been introduced to address this problem. How compounds discovered in such "binding-first" assays affect protein function, nonetheless, often remains unclear. Here, we describe a "function-first" …

    PMID 37084731 DOI ↗

  8. AKT constitutes a signal-promoted alternative exon-junction complex that regulates nonsense-mediated mRNA decay.

    Molecular cell · 2022 · 82(15): 2779-2796.e10

    Despite a long appreciation for the role of nonsense-mediated mRNA decay (NMD) in destroying faulty, disease-causing mRNAs and maintaining normal, physiologic mRNA abundance, additional effectors that regulate NMD activity in mammalian cells continue to be identified. Here, we describe a …

    PMID 35675814 DOI ↗

  9. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.

    Molecular cell · 2022 · 82(3): 645-659.e9

    Pseudouridine is a modified nucleotide that is prevalent in human mRNAs and is dynamically regulated. Here, we investigate when in their life cycle mRNAs become pseudouridylated to illuminate the potential regulatory functions of endogenous mRNA pseudouridylation. Using single-nucleotide resolution pseudouridine …

    PMID 35051350 DOI ↗

  10. Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer.

    Molecular cell · 2021 · 81(15): 3048-3064.e9

    RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function of RBPs in cancer using pooled CRISPR-Cas9 screening and identify 57 RBP candidates with distinct roles in …

    PMID 34216543 DOI ↗

  11. Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS.

    Molecular cell · 2021 · 81(9): 1905-1919.e12

    Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative …

    PMID 33852893 DOI ↗

  12. Footprinting SHAPE-eCLIP Reveals Transcriptome-wide Hydrogen Bonds at RNA-Protein Interfaces.

    Molecular cell · 2020 · 80(5): 903-914.e8

    Discovering the interaction mechanism and location of RNA-binding proteins (RBPs) on RNA is critical for understanding gene expression regulation. Here, we apply selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) on in vivo transcripts compared to protein-absent transcripts in four …

    PMID 33242392 DOI ↗

  13. Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program.

    Molecular cell · 2020 · 80(3): 452-469.e9

    Although TP53 is the most commonly mutated gene in human cancers, the p53-dependent transcriptional programs mediating tumor suppression remain incompletely understood. Here, to uncover critical components downstream of p53 in tumor suppression, we perform unbiased RNAi and CRISPR-Cas9-based genetic screens …

    PMID 33157015 DOI ↗

  14. How RNA-Binding Proteins Interact with RNA: Molecules and Mechanisms.

    Molecular cell · 2020 · 78(1): 9-29

    RNA-binding proteins (RBPs) comprise a large class of over 2,000 proteins that interact with transcripts in all manner of RNA-driven processes. The structures and mechanisms that RBPs use to bind and regulate RNA are incredibly diverse. In this review, we …

    PMID 32243832 DOI ↗

  15. A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.

    Molecular cell · 2019 · 73(2): 304-313.e3

    LIN28 RNA binding proteins are dynamically expressed throughout mammalian development and during disease. However, it remains unclear how changes in LIN28 expression define patterns of post-transcriptional gene regulation. Here we show that LIN28 expression level is a key variable that …

    PMID 30527666 DOI ↗

  16. Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.

    Molecular cell · 2018 · 70(5): 854-867.e9

    RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by …

    PMID 29883606 DOI ↗

  17. Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels.

    Molecular cell · 2018 · 69(6): 1005-1016.e7

    RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced …

    PMID 29547715 DOI ↗

  18. Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.

    Molecular cell · 2017 · 67(1): 148-161.e5

    Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational …

    PMID 28673540 DOI ↗

  19. From Protein-RNA Predictions toward a Peptide-RNA Code.

    Molecular cell · 2016 · 64(3): 437-438

    The RNA field is undergoing a renaissance, with a deluge of proteins being identified to bind RNA. Two reports now introduce proteome-wide approaches that identify the peptides that are crosslinked to RNA (Castello et al., 2016; He et al., 2016).

    PMID 27814488 DOI ↗

  20. Pairing beyond the Seed Supports MicroRNA Targeting Specificity.

    Molecular cell · 2016 · 64(2): 320-333

    To identify endogenous miRNA-target sites, we isolated AGO-bound RNAs from Caenorhabditis elegans by individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP), which fortuitously also produced miRNA-target chimeric reads. Through the analysis of thousands of reproducible chimeras, pairing to the miRNA seed emerged as …

    PMID 27720646 DOI ↗

  21. SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

    Molecular cell · 2016 · 64(2): 282-293

    RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down …

    PMID 27720645 DOI ↗

  22. Resources for the Comprehensive Discovery of Functional RNA Elements.

    Molecular cell · 2016 · 61(6): 903-13

    Transcriptome-wide maps of RNA binding protein (RBP)-RNA interactions by immunoprecipitation (IP)-based methods such as RNA IP (RIP) and crosslinking and IP (CLIP) are key starting points for evaluating the molecular roles of the thousands of human RBPs. A significant bottleneck …

    PMID 26990993 DOI ↗

  23. Blurred Boundaries: The RNA Binding Protein Lin28A Is Also an Epigenetic Regulator.

    Molecular cell · 2016 · 61(1): 1-2

    Lin28A is best known as a post-transcriptional regulator of gene expression. In this issue, Zeng et al. (2016) show that Lin28A has an unexpected role as an epigenetic regulator of DNA.

    PMID 26748607 DOI ↗

  24. Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.

    Molecular cell · 2015 · 59(3): 413-25

    RNA quality-control pathways get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the adenosine triphosphatase (ATPase) cycle of the SF1 helicase Upf1 is required for …

    PMID 26253027 DOI ↗

  25. Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing.

    Molecular cell · 2013 · 50(2): 223-35

    SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. …

    PMID 23562324 DOI ↗