ArticleScience advances2023
Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites.
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Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 28 citations in OpenAlex.
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
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- Trypanosoma cruzi cell atlas as a single-cell resource for understanding parasite population heterogeneity and differentiation.Nature communications · 2026Article
- Walnut glutelin antibacterial peptides targetFood chemistry: X · 2026Article
- Comprehensive mapping of the 5' and 3' untranslated regions ofRNA (New York, N.Y.) · 2026Article
- A Human-specific Protein Regulated by Alternative Polyadenylation Shapes Uniqueness of Human Brain Development.Genomics, proteomics & bioinformatics · 2025Article
- TDP-43 loss induces cryptic polyadenylation in ALS/FTD.Nature neuroscience · 2025Article
- Reduced Usage ofPhenomics (Cham, Switzerland) · 2025Article
- IGF2BP3 recruits NUDT21 to regulate SPTBN1 alternative polyadenylation and drive ovarian cancer progression.Communications biology · 2025Article
- Transcriptomic profiling of severe and critical COVID-19 patients reveals alterations in expression, splicing and polyadenylation.Scientific reports · 2025Article
- CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.Nature communications · 2025Article
- Article
- HIV-1-induced translocation of CPSF6 to biomolecular condensates.Trends in microbiology · 2024Review
- 2'-O-methylation at internal sites on mRNA promotes mRNA stability.Molecular cell · 2024Article
- Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA.American journal of human genetics · 2024Article
- Downregulation of CPSF6 leads to global mRNA 3' UTR shortening and enhanced antiviral immune responses.PLoS pathogens · 2024Article
- RNA binding proteins in cardiovascular development and disease.Current topics in developmental biology · 2024Article
- Infernape uncovers cell type-specific and spatially resolved alternative polyadenylation in the brain.Genome research · 2023Article
- Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing.Nature communications · 2023Article
- NUDT21 alters glioma migration through differential alternative polyadenylation of LAMC1.Journal of neuro-oncology · 2023Article
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Authors and funding
34 authors at 14 institutions in 5 countries.
Nicola de PriscoDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0001-9959-2541
Caitlin FordDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Nathan D ElrodDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.ORCID 0000-0003-1310-6026
Winston LeeDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Lauren C TangDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID 0000-0001-8786-5418
Kai-Lieh HuangDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.ORCID 0000-0001-5407-648X
Ai LinDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, WC67+HC Dongcheng, Beijing, China.ORCID 0000-0001-7502-7935
Ping JiDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.ORCID 0000-0001-7103-1507
Venkata S JonnakutiDepartment of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
Lia BoyleDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-8082-7125
Maximilian CabajDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-0133-6190
Salvatore BottaDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Katrin ÕunapDepartment of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.ORCID 0000-0002-4594-6364
Karit ReinsonDepartment of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.ORCID 0000-0001-8235-2138
Monica H WojcikBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-8162-5031
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0001-5664-7987
Weimin BiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Kristian TvetenDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.ORCID 0000-0003-1316-5843
Trine PrescottDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Thorsten GerstnerDepartment of Child Neurology and Rehabilitation and Department of Pediatrics, Hospital of Southern Norway, Arendal, Norway.ORCID 0000-0002-7035-781X
Audrey SchroederDivision of Medical Genetics, University of Rochester Medical Center, Rochester, NY, USA.ORCID 0000-0001-7836-5980
Chin-To FongDepartment of Pediatrics and of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Jaya K George-AbrahamDell Children's Medical Group, Austin, TX, USA.ORCID 0000-0001-8686-8107
Catherine A BuchananDell Children's Medical Group, Austin, TX, USA.
Andrea Hanson-KhanDepartment of Pediatrics, Division of Medical Genetics, Stanford School of Medicine, Palo Alto, CA, USA.ORCID 0000-0002-1735-5655
Jonathan A BernsteinDepartment of Pediatrics, Division of Medical Genetics, Stanford School of Medicine, Palo Alto, CA, USA.ORCID 0000-0001-5369-346X
Aikaterini A NellaJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.ORCID 0000-0003-3364-768X
Wendy K ChungDepartment of Pediatrics, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-3438-5685
Vicky BrandtDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-5512-3724
Marko JovanovicDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Kimara L TargoffColumbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY, USA.
Hari Krishna YalamanchiliJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.ORCID 0000-0001-9892-3054
Eric J WagnerDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Vincenzo A GennarinoDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-3312-6991
Columbia University Irving Medical Center · USBaylor College of Medicine · USColumbia University · USDell Children's Medical Center of Central Texas · USNeurological Research Institute · USStanford Medicine · USTartu University Hospital · EETelemark Hospital · NOThe University of Texas Medical Branch at Galveston · USUniversity of Rochester · USUniversity of Rochester Medical Center · USBroad Institute · USChinese Academy of Medical Sciences & Peking Union Medical College · CNHospital of Southern Norway · NO
Funding
Deciphering the Role of the Pumilio1 in Two Distinct Neurological DiseasesR01NS109858 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Vincenzo Alessandro Gennarino · 2019 to 2026
$4.1MExtensive multiplexing of protein nucleic-acid interactions to comprehensively study gene expression regulation from chromatin to mRNA degradationR01HG012216 · NHGRI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GUTTMAN, MITCHELL, JOVANOVIC, MARKO · 2022 to 2025
$3.1MDefining the programmed proteome rejuvenation underlying gametogenesisR01AG071869 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI BRAR, GLORIA ANN, JOVANOVIC, MARKO · 2021 to 2025
$2.9MRegulation of Protein Production Dynamics:RNA Binding Proteins and the Ribosome CodeR35GM128802 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI JOVANOVIC, MARKO · 2018 to 2022
$2.3MMechanisms of second heart field development regulated by Nkx genesR01HL131438 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TARGOFF, KIMARA L · 2017 to 2021
$2.1MMechanisms of outflow tract morphogenesis regulated by extracellular matrixR01HL170188 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KIMARA L TARGOFF · 2023 to 2026
$2.1MMechanisms of myocardial regeneration mediated by Nkx2.5 in zebrafishR01HL162989 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KIMARA L TARGOFF · 2023 to 2026
$2.0MNHGRI NIH HHS R01 HG012216NHLBI NIH HHS R01 HL131438NHLBI NIH HHS R01 HL162989NHLBI NIH HHS R01 HL170188NIA NIH HHS R01 AG071869NIGMS NIH HHS R35 GM128802NINDS NIH HHS R01 NS109858
Abstract
Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, here, we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function mostly undergo 3'UTR APA and are up-regulated. This suggests that, under healthy conditions, cells toggle between internal and 3'UTR APA to modulate protein expression.
Indexed as
PolyadenylationZebrafish3' Untranslated RegionsAnimalsEmbryo, NonmammalianExonsHumansInfant, NewbornIntronsmRNA Cleavage and Polyadenylation Factors3' Untranslated Regionscleavage factor Im, humanmRNA Cleavage and Polyadenylation Factors
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.