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Record W4402622603 · doi:10.1016/j.molcel.2024.08.010

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

2024· article· en· W4402622603 on OpenAlexafffund
Maya L. Gosztyla, Lijun Zhan, Sara Olson, Xintao Wei, Jack T. Naritomi, Grady G. Nguyen, Lena Annika Street, Grant A. Goda, Francisco F. Cavazos, Jonathan C. Schmok, Manya Jain, Easin Uddin Syed, Eun‐Jeong Kwon, Wenhao Jin, Eric Kofman, Alexandra Tankka, Allison Li, Valerie Gonzalez, Éric Lécuyer, Daniel Dominguez, Marko Jovanović, Brenton R. Graveley, G Yeo

Bibliographic record

VenueMolecular Cell · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsMontreal Clinical Research Institute
FundersNational Institute of General Medical SciencesNational Human Genome Research InstituteNational Institute of Mental HealthNational Institute on AgingFonds de Recherche du Québec - SantéUniversity of California, San DiegoNatural Sciences and Engineering Research Council of CanadaNational Science FoundationCanadian Institutes of Health ResearchChan Zuckerberg InitiativeAssociation for Women in ScienceMyotonic Dystrophy FoundationNational Cancer InstituteNational Sleep FoundationNational Institutes of Health
KeywordsBiologyZinc fingerComputational biologyRNAOmicsRNA-binding proteinCell biologyBioinformaticsGeneticsGeneTranscription factor

Abstract

fetched live from OpenAlex

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 regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation. The examined ZFPs show widespread sequence-specific RNA binding and preferentially bind proximal to transcription start sites. Additionally, several ZFPs associate with their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DNA/RNA-associated protein that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.067
Threshold uncertainty score0.451

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.256
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations41
Published2024
Admission routes2
Has abstractyes

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